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CORK Bibliography: Laboratory Tests for Drug Use

45 citations. January 2009 to present

Prepared: December 2011

Allemann D; Pauli H; Murner A; Steiner S; Helmlin HJ. HPLC on the dance floor. Chimia 64(9-10): 668-668, 2010. (0 refs.)

Note: HPLC is an instrument used in drug testing.

Anderson JM. Evaluating the athlete's claim of an unintentional positive urine drug test. (review). Current Sports Medicine Reports 10(4): 191-196, 2011. (28 refs.)

During a urine drug testing program, an athlete may make a claim that the results of a positive test have arisen from factors that were out of his or her control, and therefore, he or she should not be held responsible for the results. Some of these claims may include classic claims of passive inhalation of marijuana smoke or ingestion of poppy seeds leading to positive tests. In addition, with the proliferation of nutritional supplements on the market, many athletes claim that they accidentally ingested a banned substance contained in one of these. It is important that any sports medicine physician involved with sports drug testing be informed of the data that either support or refute these claims and that he or she contribute to a program wherein adequate education and policy establishment help to limit the likelihood of such claims. This article will review the data to help address these claims.

Ashford KB; Hahn E; Hall L; Rayens MK; Noland M; Collins R. Measuring prenatal secondhand smoke exposure in mother-baby couplets. Nicotine & Tobacco Research 12(2): 127-135, 2010. (48 refs.)

Introduction: Pregnant women often underreport their smoking status and extent of secondhand smoke (SHS) exposure. Biomarker confirmation is the recommended method to assess smoking behaviors and SHS exposure in both mothers and infants. Objectives: The primary aims are to (a) examine the relationship between smoking behaviors and SHS exposure in mother-baby couplets using maternal and infant hair nicotine and maternal urine cotinine analyses and (b) determine whether there is an association between maternal and infant hair nicotine samples obtained shortly after birth. Discussion: A cross-sectional study with a multiethnic sample of 210 mother-baby couplets assessing SHS exposure. Results: The level of maternal hair nicotine (MHN) was significantly different among three groups: nonsmoking, nonsmoking/passive exposed, and smoking (p < .0001), with nonsmoking and nonexposed women having the lowest level. Urine cotinine was strongly associated with self-reported smoking status (rho = .88; p < .0001). Maternal and infant hair nicotine were correlated, although MHN correlated more strongly with smoking status (rho = .46, p < .0001) than infant hair nicotine (rho = .39, p < .0001). Conclusions: MHN was a more precise biomarker of prenatal SHS exposure than infant hair nicotine; mothers' urine cotinine was strongly correlated with self-reported smoking status.

Been F; Roggo Y; Degardin K; Esseiva P; Margot P. Profiling of counterfeit medicines by vibrational spectroscopy. Forensic Science International 211(1-3): 83-100, 2011. (35 refs.)

Counterfeit pharmaceutical products have become a widespread problem in the last decade. Various analytical techniques have been applied to discriminate between genuine and counterfeit products. Among these, near-infrared (NIR) and Raman spectroscopy provided promising results. The present study offers a methodology allowing to provide more valuable information for organisations engaged in the fight against counterfeiting of medicines. A database was established by analyzing counterfeits of a particular pharmaceutical product using Near-infrared (NIR) and Raman spectroscopy. Unsupervised chemometric techniques (i.e. principal component analysis - PCA and hierarchical cluster analysis - HCA) were implemented to identify the classes within the datasets. Gas Chromatography coupled to Mass Spectrometry (GC-MS) and Fourier Transform Infrared Spectroscopy (FT-IR) were used to determine the number of different chemical profiles within the counterfeits. A comparison with the classes established by NIR and Raman spectroscopy allowed to evaluate the discriminating power provided by these techniques. Supervised classifiers (i.e. k-Nearest Neighbors, Partial Least Squares Discriminant Analysis, Probabilistic Neural Networks and Counterpropagation Artificial Neural Networks) were applied on the acquired NIR and Raman spectra and the results were compared to the ones provided by the unsupervised classifiers. The retained strategy for routine applications, founded on the classes identified by NIR and Raman spectroscopy, uses a classification algorithm based on distance measures and Receiver Operating Characteristics (ROC) curves. The model is able to compare the spectrum of a new counterfeit with that of previously analyzed products and to determine if a new specimen belongs to one of the existing classes, consequently allowing to establish a link with other counterfeits of the database.

Bell C; George C; Kicman AT; Traynor A. Development of a rapid LC-MS/MS method for direct urinalysis of designer drugs. Drug Testing and Analysis 3(7-8, special issue): 496-504, 2011. (37 refs.)

The current immunoassay screening methodologies used to detect sympathomimetic amines within the context of workplace drug testing may fail to detect a number of the emerging designer drugs, for example beta-keto amphetamines and piperazine derivatives, commonly referred to as 'legal highs'. Therefore, a rapid multi-analyte qualitative screening method, using ultra-high-pressure liquid chromatography-tandem mass spectrometry (LC-MS/MS), was investigated for analysis of new designer drugs that have emerged from the former legal highs market. Eight analytes were targeted as model compounds: 4-methylmethcathinone (mephedrone), 3,4-methylenedioxymethcathinone (bk-MDMA, 'methylone'), 2-methylamino-1-(3,4-methylenedioxyphenyl)butan-1-one (bk-MBDB, 'butylone'), 4-methoxymethcathinone (bk-PMMA, 'methedrone'), 1-benzylpiperazine (BZP), 1-(3-trifluoromethyl phenyl)-piperazine (TFMPP), 1-(3-chloro phenyl)-piperazine (mCPP), and 3, 4-methylenedioxypyrovalerone (MDPV). The LC-MS/MS method developed encompassed direct analysis following a 1 : 4 dilution of urine with mobile phase to reduce matrix effects. Although not all compounds were completely resolved chromatographically, two product ions conferred sufficient specificity to allow target analyte identification. Although all target analytes were readily detected at 500 ng/ml, a cut-off of 1000 ng/ml was chosen to mirror the amphetamine screening cut-off commonly used for routine analysis of workplace drug testing samples. In conclusion, direct analysis using LC-MS/MS offers an attractive way forward for the development of a rapid routine screen for new psychoactive substances, particularly given the growing number of novel compounds.

John Wiley & Sons

Benowitz NL; Dains KM; Dempsey D; Yu LS; Jacob P. Estimation of nicotine dose after low-level exposure using plasma and urine nicotine metabolites. Cancer Epidemiology, Biomarkers & Prevention 19(5): 1160-1166, 2010. (11 refs.)

Background: We sought to determine the optimal plasma and urine nicotine metabolites, alone or in combination, to estimate the systemic dose of nicotine after low-level exposure. Methods: We dosed 36 nonsmokers with 100, 200, or 400 mu g p.o. of deuterium-labeled nicotine (doses similar to exposure to secondhand smoke) daily for 5 days and then measured plasma and urine nicotine metabolites at various intervals over 24 hours. Results: The strongest correlations with nicotine dose were seen for the sum of four (cotinine + cotinine-glucuronide + trans-3'-hydroxycotinine + 3HC-glucuronide) or six (including also nicotine + nicotine-glucuronide) of the major nicotine metabolites in 24-hour urine collection (r = 0.96), with lesser correlations for these metabolites using spot urines corrected for creatinine at various times of day (r = 0.72-0.80). The sum of plasma cotinine + trans-3'-hydroxycotine was more highly correlated with nicotine dose than plasma cotinine alone (r = 0.82 versus 0.75). Conclusions: Our results provide guidance for the selection of biomarkers to estimate the dose of nicotine taken in low-level (secondhand smoke) tobacco exposure. Impact: This is probably relevant to active smoking as well.

Benowitz NL; Dains KM; Dempsey D; Havel C; Wilson M; Jacob P. Urine menthol as a biomarker of mentholated cigarette smoking. Cancer Epidemiology, Biomarkers & Prevention 19(12): 3013-3019, 2010. (26 refs.)

Objectives: Menthol cigarettes are smoked by 27% of U. S. smokers, and there are concerns that menthol might enhance toxicity of cigarette smoking by increasing systemic absorption of smoke toxins. We measured urine menthol concentrations in relation to biomarkers of exposure to nicotine and tobacco carcinogens. Methods: Concentrations of menthol glucuronide (using a novel analytical method), nicotine plus metabolites (nicotine equivalents, NE), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and polycyclic aromatic hydrocarbon (PAH) metabolites were measured in the urine of 60 menthol and 67 regular cigarette smokers. Results: Urine menthol was measurable in 82% of menthol and 54% in regular cigarette smokers. Among menthol smokers, urine menthol was highly correlated with NE, NNAL, and PAHs. In a multiple regression model NE but not menthol was significantly associated with NNAL and PAHs. Conclusions: Urine menthol concentration is a novel biomarker of exposure in menthol cigarette smokers, and is highly correlated with exposure to nicotine and carcinogens. Menthol is not independently associated with carcinogen exposure when nicotine intake is considered.

Bright RP; Civalier KM; Krahn L. Reliability of self-reported nicotine use as determined by serum cotinine levels in patients referred for liver transplantation. Psychosomatics 51(5): 395-400, 2010. (29 refs.)

Background: Smoking has been associated with a higher incidence of post-hepatic transplantation de novo noncutaneous neoplasms and vascular complications. There are conflicting reports regarding increased posttransplant mortality. Objective: The authors sought to determine the reliability of patient-reported nicotine product use (NPU) in candidates for hepatic transplantation. Method: The authors performed a retrospective chart review of all patients referred for liver transplantation in a 12-month period. Each patient's report of recent or current nicotine product use through smoking, chewing tobacco, or nicotine replacement products, as obtained in interviews, was compared with the quantitative result of serum cotinine levels. Results: Of 171 patients referred for liver transplant evaluation during a 12-month period, 17% reported ongoing NPU, and 83% denied it. Of the patients who denied recent NPU, 11% had serum cotinine levels reflective of active use. Of the patients reporting active NPU, 97% had positive cotinine levels. Conclusion: There was a high degree of reliability of patient self-reported NPU, but detecting deceptive reporting is important in the selection of patients who will have long-term success with liver transplantation.

Canfield DV; Dubowski KM; Whinnery JE; Lewis RJ; Ritter RM; Rogers PB. Increased cannabinoids concentrations found in specimens from fatal aviation accidents between 1997 and 2006. Forensic Science International 197(1-3): 85-88, 2010. (24 refs.)

The National Institute on Drug Abuse (NIDA) and the Office of National Drug Control Policy (ONDCP) reported a 1.5-fold increase in the delta-9-tetrahydrocannabinol (THC) content of street cannabis seizures from 1997 to 2001 versus 2002 to 2006. This study was conducted to compare the changes, over those years, in blood and urine cannabinoid concentrations with the potency of THC reported in the cannabis plant. Cannabinoids were screened using radioimmunoassay (RIA) for blood and fluorescence polarization immunoassay (FPIA) for urine and confirmed using GC/MS. A total of 95 individuals were found to be using cannabis from a total number of 2769 (3.4%) individuals tested over the period 1997 through 2006. Other impairing drugs were found in 38% of the cannabinoids-positive individuals. The mean concentration of THC in blood for 1997-2001 was 2.7 ng/mL; for 2002-2006, it was 7.2 ng/mL, a 2.7-fold increase in the mean THC concentration of specimens from aviation fatalities, compared to a 1.5-fold increase in cannabis potency reported by the NIDA and ONDCP. The mean age for cannabis users was 40 years (range 18-72) for aviation fatalities. For all blood and urine specimens testing negative for cannabinoids from aviation fatalities, the mean age of the individuals was 50 years (range 14-92). More than half of the fatalities tested were 50 years or older, whereas, 80% of the positive cannabis users were under 50. As indicated by these findings, members of the transportation industry, government regulators, and the general public should be made aware of the increased potential for impairment from the use of high-potency cannabis currently available and being used.

Caraballo RS; Holiday DB; Stellman SD; Mowery PD; Giovino GA; Muscat JE et al. Comparison of serum cotinine concentration within and across smokers of menthol and nonmenthol cigarette brands among Non-Hispanic Black and Non-Hispanic White US adult smokers, 2001-2006. Cancer Epidemiology, Biomarkers & Prevention 20(7): 1329-1340, 2011. (36 refs.)

Background: The Food and Drug Administration (FDA) is examining options for regulating menthol content in cigarettes. There are many pharmacologic properties of menthol that may facilitate exposure to tobacco smoke, and it has been suggested that the preference for menthol cigarettes in black smokers accounts for their higher cotinine levels. Objective: To assess cigarettes smoked per day-adjusted cotinine levels in relation to smoking a menthol or nonmenthol cigarette brand among non-Hispanic black and white U. S. adult smokers under natural smoking conditions. Method: Serum cotinine concentrations were measured in 1,943 smokers participating in the 2001 to 2006 National Health and Nutrition Examination Surveys (NHANES). The effect of smoking a menthol brand on cigarettes smoked per day-adjusted serum cotinine levels in these two populations was modeled by adjusting for sex, age, number of smokers living in the home, body weight, time since last smoked, and FTC (Federal Trade Commission)-measured nicotine levels. The 8- or 12-digit Universal Product Code (UPC) on the cigarette label was used to determine the cigarette brand and whether it was menthol. Results: Smoking a menthol cigarette brand versus smoking a nonmenthol cigarette brand was not associated (P >= 0.05) with mean serum cotinine concentration in either black or white smokers. Conclusions: The higher levels of cotinine observed in black smokers compared with white smokers are not explained by their higher preference for menthol cigarette brands. Impact: Further studies like ours are needed to improve our ability to understand health consequences of future changes in tobacco product design.

Chambers DM; Ocariz JM; McGuirk MF; Blount BC. Impact of cigarette smoking on volatile organic compound (VOC) blood levels in the U.S. Population: NHANES 2003-2004. Environment International 37(8): 1321-1328, 2011. (25 refs.)

The impact of cigarette smoking on volatile organic compound (VOC) blood levels is studied using 2003-2004 National Health and Nutrition Examination Survey (NHANES) data. Cigarette smoke exposure is shown to be a predominant source of benzene, toluene, ethylbenzene, xylenes and styrene (BTEXS) measured in blood as determined by (1) differences in central tendency and interquartile VOC blood levels between daily smokers [>= 1 cigarette per day (CPD)] and less-than-daily smokers, (2) correlation among BTEXS and the 2,5-dimethylfuran (2,5-DMF) smoking biomarker in the blood of daily smokers, and (3) regression modeling of BTEXS blood levels versus categorized CPD. Smoking status was determined by 2,5-DMF blood level using a cutpoint of 0.014 ng/ml estimated by regression modeling of the weighted data and confirmed with receiver operator curve (ROC) analysis. The BTEXS blood levels among daily smokers were moderately-to-strongly correlated with 2,5-DMF blood levels (correlation coefficient, r, ranging from 0.46 to 0.92). Linear regression of the geometric mean BTEXS blood levels versus categorized CPD showed clear dose-response relationship (correlation of determination, R-2, ranging from 0.81 to 0.98). Furthermore, the pattern of VOCs in blood of smokers is similar to that reported in mainstream cigarette smoke. These results show that cigarette smoking is a primary source of benzene, toluene and styrene and an important source of ethylbenzene and xylene exposure for the U.S. population, as well as the necessity of determining smoking status and factors affecting dose (e.g.. CPD, time since last cigarette) in assessments involving BTEXS exposure.

Chappell JS; Lee MM. Cathinone preservation in khat evidence via drying. Forensic Science International 195(1/3): 108-120, 2010. (23 refs.)

A primary concern with the forensic analysis of the khat plant (Catha edulis) has been the need to preserve the principle psychoactive component, cathinone, which converts to the less-active substance, cathine, after harvesting. The loss of cathinone has serious legal implications since it is a Schedule I controlled substance under federal regulations in the United States, while cathine is Schedule IV. A common misconception is that cathinone is highly unstable once the plant is harvested, and may be undetectable upon drying and prolonged storage. However, drying the plant material will preserve cathinone. Numerous seizures of a dried form of khat (referred to as "graba" in the United States) have been made in recent years, suggesting that drying the plant material is a viable approach to preserve khat evidence for both storage and reanalysis. A qualitative and quantitative study of the composition of khat samples seized as dried plant material has found the khat alkaloids to be relatively stable for a monitored period of 3 years, and cathinone has remained identifiable while stored at room temperature for over 10 years. Studies of green khat (received moist) have also determined that drying the moist leaves at either room temperature or by the application of heat are suitable methods to preserve cathinone in the dried material. These findings demonstrate that cathinone persists in dried khat for a time frame of several years, and simple drying techniques are an effective means to preserve seized khat evidence for long-term storage.

Christensen SE. Health promotion and human right protection: Finding a balance for HIV testing policies in US state prisons. Journal of the Association of Nurses in AIDS Care 22(3): 238- 243, 2011. (25 refs.)

In 2008, approximately 1.5 million people were reported to be incarcerated in a prison in the United States (Maruschak, 2009). Previous research has shown that many incarcerated individuals engage in high-risk sexual behaviors and/or have a history of substance abuse (Centers for Disease Control and Prevention [CDC], n.d., para. 2), thereby putting them in a high-risk group for contracting HIV infection. As one would expect, this high-risk behavior has translated into startling statistics. According to the most recent U.S. Bureau of Justice report, the number of HIV-infected individuals living in the United States who are incarcerated is approximately 2.5 times higher than that of the general population (Maruschak, 2009). What is even more alarming is the fact that many of the infected individuals are unaware of their HIV status at the time of incarceration (Desai, Latta, Spaulding, Rich, & Flanigan, 2002). In addition to the high-risk behaviors engaged in by many of those who enter prison before their incarceration, once an individual is established within the prison setting, high-risk behaviors often continue. Many studies have examined the incidence of sexual activity in prisons; however, the results have been far from conclusive. Saum, Surratt, Inciardi, and Bennett (1995) reported a rate of 2%, whereas an earlier survey that was conducted when HIV was a newly emerging and unknown infection estimated a much higher rate of 65% (Wooden & Parker, 1982).

Christo PJ; Manchikanti L; Ruan XL; Bottros M; Hansen H; Solanki DR et al. Urine drug testing in chronic pain. (review). Pain Physician 14(2): 123-143, 2011. (220 refs.)

Therapeutic use, overuse, abuse, and diversion of controlled substances in managing chronic non-cancer pain continue to be an issue for physicians and patients. The challenge is to eliminate or significantly curtail abuse of controlled prescription drugs while still assuring the proper treatment of those patients. Some physicians are apprehensive regarding the use of chronic opioid therapy in chronic non-cancer pain due to a perceived lack of proven evidence, the misuse of opioids, tolerance, dependence, and hyperalgesia. However, others have criticized the underuse of opioids, resulting in the undertreatment of pain. It has been the convention that federal, state, and local governments; professional associations; as well as pharmaceutical companies, physicians, accrediting bodies, medical licensure boards, and the public all share responsibility for preventing abuse of controlled prescription drugs. To overcome the critical challenge of eliminating or significantly curtailing abuse of controlled prescription drugs and at the same time assuring the appropriate treatment for those patients who can be helped by these medications, it is crucial to practice adherence or compliance monitoring of opioid therapy. Compliance monitoring has been shown to be crucial in delivering proper opioid therapy and preserving this therapy for the future. Urine drug testing (UDT) is considered one of the mainstays of adherence monitoring in conjunction with prescription monitoring programs and other screening tools, however, UDT is associated with multiple limitations secondary to potential pitfalls related to drug metabolism, reliability of the tests, and the knowledge of the pain physician. UDT is a widely available and familiar method for monitoring opioid use in chronic pain patients. UDT can provide tools for tracking patient compliance and expose possible drug misuse and abuse. UDT is one of the major tools of adherence monitoring in the assessment of the patient's predisposition to, and patterns of, drug misuse/abuse a vital first step towards establishing and maintaining the safe and effective use of opioid analgesics in the treatment of chronic pain. This comprehensive review provides the role of UDT in monitoring chronic opioid therapy along with reliability and accuracy, appropriate use, overuse, misuse, and abuse.

Colon HM; Perez CM; Melendez M; Marrero E; Ortiz AP; Suarez E. The validity of drug use responses in a household survey in Puerto Rico: Comparison of survey responses with urinalysis. Addictive Behaviors 35(7): 667-672, 2010. (36 refs.)

Aims: The available evidence suggests that the validity of drug use responses in general population surveys is low. We have conducted a household survey to examine viral infections in the general population of Puerto Rico employing a number of procedures believed to increase the validity of drug use responses, as well as confidentiality and privacy: Telling participants of toxicological verification of drug use prior to the interview, ACASI self-interviewing, and interviewing outside households in mobile examination units. Methods: The study employed a stratified cluster sample of 1654 adults 21 to 64 years old, 532 recruited while urine samples were being collected and 1122 recruited after urinalysis was discontinued due to budgetary reasons. Results: Drug use rates calculated from participants recruited while urinalysis was being conducted did not vary significantly to those derived from participants recruited after urinalysis was discontinued. Sensitivity of responses of drug use during the last three days was 80.0% for marihuana, 76.2% for cocaine, and 40.0% for heroin. The lower validity of heroin reports did not seem to be the result of underreporting as it was reported by more individuals than the test detected. Conclusion: We conjecture that the reasonably good validity of the drug use responses might have been the result of the parent study being about a health issue other than drug use, and that interviewing was conducted outside households in mobile units. These findings buttress the value of conducting methodological trials to identify procedures which yield valid responses of drug use.

De Letter EA; Stove CP; Lambert WE; Piette MHA. Post-mortem (re)distribution of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"): Human and animal data. (review). Current Pharmaceutical Biotechnology 11(5): 453-459, 2010. (112 refs.)

In this paper, the distribution and redistribution of the amphetamine derivative, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is brought into focus. Animal experimental data were compared with internationally reported MDMA-related human fatalities: in general, these turned out to be parallel with each other. Due to its inherent properties (e. g. significant volume of distribution), MDMA is liable to postmortem redistribution. Indeed, very high concentrations have been found in cardiac blood and tissues located centrally in the body (blood-rich organs such as lungs and liver in particular). This confirms that post-mortem redistribution due to diffusion from higher to lower concentration can easily take place, mainly at longer post-mortem intervals and when putrefaction occurs. Therefore, we can conclude that for post-mortem quantitation of amphetamine and derivatives, and MDMA in particular, peripheral blood sampling (e. g. femoral vein) remains compulsory. However, if the latter is impossible, MDMA quantification in a few alternative matrices such as vitreous humour and iliopsoas muscle may provide additional information to come to a reliable conclusion. Furthermore, it should be stressed that - at present - it is impossible to estimate the individual susceptibility to the various possible adverse effects of MDMA, which implies that it is impossible to provide a "safe" or "therapeutic" blood MDMA level. Therefore, in current forensic practice, the post-mortem pathological and toxicological findings should form an entity in order to draw a well-grounded conclusion.

Debruyne D; Courne MA; Le Boisselier R; Djezzar S; Gerardin M; Boucher A et al. Mephedrone: A designer drug of recent use in France. Therapie 65(6): 519-524, 2010. (16 refs.)

Designer drugs are currently marketed as substitutes for stimulant drugs as cocaine, amphetamine, MDMA. Unlike compounds listed as narcotics, these new substances are deliberately synthesized to avoid anti-drug laws. Among them, mephedrone (4-methylmethcatinone) that belongs to cathinone family, has been recently introduced in France. Users report positive euphoric and entactogenic effects. They also describe negative effects such as increased dependence towards the drug itself and larger craving for tobacco and alcohol. The numerous and various described adverse effects include psychoactive, digestive, cardiovascular... effects. Some fatality cases have been reported in scientific literature or in press and attributed to mephedrone often in association with other substances. Mephedrone has been listed as narcotic in several European countries and more recently in France.

Donike M. The detection of doping by means of chromatographic methods. Drug Testing and Analysis 3(1): 15-17, 2011. (14 refs.)

This article was first published in German in Der Sportarzt, 1966, 2, 81-84 as Der Dopingnachweis mit Hilfe chromatographischer Methoden. Translated and republished with permission. Doping has become an issue in elite sport and necessitates sensitive detection assays that enable the identification of organic compounds on a microscale level in urine. In agreement with modern toxicological methods, sports drug testing approaches can utilize paper, thin layer or gas chromatographic methods to reveal the presence of prohibited substances such as strychnine, pervitine, captagone, benzedrine etc. in doping control specimens. Basic principles of these strategies are summarized and considerations for future applications discussed.

El Marroun H; Tiemeier H; Jaddoe VWV; Hofman A; Verhulst FC; van den Brink W et al. Agreement between maternal cannabis use during pregnancy according to self-report and urinalysis in a population-based cohort: The Generation R Study. European Addiction Research 17(1): 37-43, 2011. (34 refs.)

Aim: To verify self-reported information on prenatal drug use in urine because reporting in pregnancy is sensitive to stigma and might lead to misclassification. Methods: Using semiquantitative immunochemical analysis, the presence of the urinary metabolite (11-nor-Delta 9-tetrahydrocannabinol-9-carboxylic acid) was compared to self-reported prenatal cannabis use. Sensitivity and specificity for self-report and urinalysis outcomes were calculated and Yule's Y was used as an agreement measure. Results: Urine samples were available for 3,997 pregnant women. Of these women, 92 reported having used cannabis during pregnancy (2.3%) and 71 had positive urine screens (1.8%). In total 35% of the 92 women with self-reported cannabis use also had a positive urine screen. Positive urines were relatively frequent in women reporting cannabis use before pregnancy only (7.6%) and in women with missing information (2.6%). Sensitivity and specificity of urinalysis compared to self-report were 0.46 and 0.98. Sensitivity and specificity of self-report compared to urinalysis were 0.36 and 0.99. Yule's Y amounted to 0.77, indicating substantial agreement between the measures. Conclusions: Our findings illustrate the difficulties in obtaining valid information on prenatal cannabis use. To improve the quality of cannabis use data, we suggest a 2-step approach starting with self-report.

El Marroun H; Tiemeier H; Jaddoe VWV; Hofman A; Verhulst FC; van den Brink W et al. Agreement between maternal cannabis use during pregnancy according to self-report and urinalysis in a population-based cohort: The Generation R Study. European Addiction Research 17(1): 37-43, 2011. (34 refs.)

El-Haj BM; Ali HS; Hamoudi NM. Oripavine as a new marker of opiate product use. Forensic Toxicology 29(2): 152-158, 2011. (21 refs.)

During our extensive surveillance of opiates in urine specimens of opium users, we noticed the appearance of an unknown peak (compound X) in total ion chromatograms obtained by gas chromatography-mass spectrometry (GC-MS) after enzymatic hydrolysis and trimethylsilyl (TMS) derivatization. We identified the compound X as oripavine. Oripavine was found to be a new and useful putative marker of opium/poppy seed use in differentiation from heroin, pharmaceutical codeine, and pharmaceutical morphine use. The presence of oripavine in the urine of opium users is probably the result of O-demethylation of the opium alkaloid thebaine. Analytical method optimization for GC-MS detection of oripavine in urine was also undertaken. Underivatized oripavine could not be detected by GC-MS, and trials for derivatization of oripavine with acetic anhydride and propionic anhydride were unsuccessful. Trials were successful with bis(trimethylsilyl)trifluoroacetamide/trimethylchlorosilane. It was also disclosed that almost all amounts of oripavine in human urine existed in the unconjugated form; it was absolutely necessary to hydrolyze the conjugate before TMS derivatization of oripavine for its GC-MS analysis.

Erdemir EO; Sonmez IS; Oba AA; Bergstrom J; Caglayan O. Periodontal health in children exposed to passive smoking. Journal of Clinical Periodontology 37(2): 160-164, 2010. (41 refs.)

Aim: To determine (1) the cotinine levels of saliva, urine and gingival crevicular fluid (GCF) of children in families with and without smoking members and (2) a possible association between the periodontal health of the children and exposure to passive smoking. Material and Methods: The study population comprised of 109 children in the age range 6-12 years. Children were classified as exposed to passive tobacco smoking (PTS-exposed, n=51) and as unexposed controls (PTS-unexposed, n=58). Plaque index, gingival index, bleeding on probing, probing depth and clinical attachment level (CAL) were recorded. GCF, saliva and urine samples were also collected. The levels of cotinine in these fluids were determined by enzyme-linked immunosorbent assay. Results: The mean salivary cotinine concentration was significantly increased in PTS-exposed children compared with PTS-unexposed children (p < 0.05). Further, in a dose-dependent way, the mean salivary concentration was significantly higher in children whose father or mother was a smoker (p < 0.05) as compared, respectively, with children whose fathers and mothers were non-smokers. The mean CAL was significantly less in PTS-exposed children compared with non-PTS-exposed children (0.09 mm; p < 0.05) and also in children whose father was a smoker (p < 0.05), but not in children whose mother was a smoker as compared with non-smoker fathers and mothers, respectively. The GCF cotinine levels were below the detection limits with the assay method that was used. Conclusions: We have observed that children who are exposed to passive smoking have elevated cotinine levels in their saliva concomitant with a lowered CAL.

Esseiva P; Gaste L; Alvarez D; Anglada F. Illicit drug profiling, reflection on statistical comparisons. Forensic Science International 207(1-3): 27-34, 2011. (16 refs.)

This paper presents reflexions about statistical considerations on illicit drug profiling and more specifically about the calculation of threshold for determining of the seizure are linked or not. The specific case of heroin and cocaine profiling is presented with the necessary details on the target profiling variables (major alkaloids) selected and the analytical method used. Statistical approach to compare illicit drug seizures is also presented with the introduction of different scenarios dealing with different data pre-treatment or transformation of variables. The main aim consists to demonstrate the influence of data pre-treatment on the statistical outputs. A thorough study of the evolution of the true positive rate (TP) and the false positive rate (FP) in heroin and cocaine comparison is then proposed to investigate this specific topic and to demonstrate that there is no universal approach available and that the calculations have to be revaluate for each new specific application.

Fidler JA; Stapleton JA; West R. Variation in saliva cotinine as a function of self-reported attempts to reduce cigarette consumption. Psychopharmacology 217(4): 587-593, 2011. (22 refs.)

Rationale: Cotinine is an accurate objective marker of nicotine intake. There is very little information on its stability over time or as a function of self-reported attempts at smoking reduction. Objectives: This study aimed to assess the stability of saliva cotinine concentrations over a 3-month period, as a function of self-reported attempts to reduce cigarette consumption, using data from a general population sample of English smokers. Methods: Six-hundred and ninety-one smokers from a population sample of English smokers provided saliva samples for cotinine analysis on two occasions 3 months apart. Data on cigarette consumption, whether smokers reported that they were attempting to cut down consumption and concurrent use of nicotine replacement therapy (NRT), were also collected on both occasions. Results The 'test-retest' measure of cotinine stability was 0.76, and the simple correlation was 0.73. Smokers not using NRT who reported cutting down on one occasion but not the other showed a small reduction in cigarette consumption at the time they were cutting down (1.1 cig per day, p=0.013) but no significant difference in saliva cotinine concentrations (mean reduction=13.4 ng/ml, p=0.39). Conclusions: Saliva cotinine concentrations show moderate-to-high stability within subjects over a 3-month period. Smokers' reports of attempting to cut down their smoking are associated with small daily cigarette consumption decreases but no detectable change in nicotine intake.

Fu M; Martinez-Sanchez JM; Agudo A; Pascual JA; Borras JM; Samet JM et al. Association between time to first cigarette after waking up and salivary cotinine concentration. Nicotine & Tobacco Research 13(3): 168-172, 2011. (24 refs.)

The time to first cigarette smoked after waking up appears to be a good predictor of plasma and urine cotinine levels; however, collection of blood and urine is difficult in population-based studies and may influence participation. We aimed to test whether time to first cigarette is associated with salivary cotinine. We used data from a cross-sectional study on a representative sample of the general population of Barcelona, Spain. We gathered information on smoking by means of a questionnaire and collected saliva for cotinine analysis. Of 1,245 participants, 22.9% were daily smokers, and the final sample for analysis consisted of 210 daily smokers. There were significant associations between salivary cotinine and time to first cigarette, between cigarette consumption and time to first cigarette, and between salivary cotinine and cigarette consumption. Salivary cotinine had decreased as time to first cigarette increased. After adjusting for cigarette consumption and sex, there were significant differences in mean salivary cotinine according to time to first cigarette (< 5 min: 219.2 ng/ml; 6-30 min: 175.8 ng/ml; 31-60 min: 168.5 ng/ml; > 60 min: 137.2 ng/ml). All paired comparisons were significant (p < .001) except in the 6- to 30-min group versus the 31- to 60-min group (p = .701). After adjustment for the number of cigarettes smoked in the last 24 hr, time to first cigarette is associated with salivary cotinine concentration.

Gjerde H; Normann PT; Christophersen AS; Morland J. Prevalence of driving with blood drug concentrations above proposed new legal limits in Norway: Estimations based on drug concentrations in oral fluid. Forensic Science International 210(1-3): 221-227, 2011. (44 refs.)

Aim: To estimate the prevalence of driving with blood drug concentrations above the recently proposed Norwegian legal limits for drugged driving in random traffic. The results from a roadside survey of 10,816 drivers was used as basis for the estimation, and the most prevalent drugs were included. Methods: Three approaches were used to estimate the prevalence of drug concentrations above the proposed legal limits in blood based on drug concentrations in oral fluid: comparison with drug concentrations observed in oral fluid and blood in pharmacokinetic studies, estimating the prevalence of drug concentrations in blood by calculating the prevalence of drug concentrations in oral fluid that were larger than the limit in blood multiplied with mean oral fluid/blood ratios, and a mathematical simulation mimicking the relationship between drug concentration distributions in blood and oral fluid for populations of drug users. Results: In total, alcohol or drugs were detected in 5.7% of the samples of oral fluid from drivers in normal traffic; 3.8% (n = 410) were positive for the drugs that we included in the assessment. The estimation of drug concentrations in blood suggested that about 1.5% had concentrations above the proposed legal limits in blood for the studied drugs, which is about 40% of those who were positive for the drugs in oral fluid. Conclusion: The estimated prevalence of driving with concentrations of psychoactive drugs in blood above the proposed legal limits was for illegal drugs 0.4% and for medicinal drugs 1.1%. These may be regarded as minimum estimates as some drugs were not included in the assessment. These prevalences are higher than the prevalence of driving with blood alcohol concentrations above the legal limit of 0.2 g/kg in Norway.

Gjerde H; Verstraete A. Can the prevalence of high blood drug concentrations in a population be estimated by analysing oral fluid? A study of tetrahydrocannabinol and amphetamine. Forensic Science International 195(1-3): 153-159, 2010. (20 refs.)

Aim: To study several methods for estimating the prevalence of high blood concentrations of tetrahydrocannabinol and amphetamine in a population of drug users by analysing oral fluid (saliva). Methods: Five methods were compared, including simple calculation procedures dividing the drug concentrations in oral fluid by average or median oral fluid/blood (OF/B) drug concentration ratios or linear regression coefficients, and more complex Monte Carlo simulations. Populations of 311 cannabis users and 197 amphetamine users from the Rosita-2 Project were studied. Results: The results of a feasibility study suggested that the Monte Carlo simulations might give better accuracies than simple calculations if good data on OF/B ratios is available. If using only 20 randomly selected OF/B ratios, a Monte Carlo simulation gave the best accuracy but not the best precision. Dividing by the OF/B regression coefficient gave acceptable accuracy and precision, and was therefore the best method. None of the methods gave acceptable accuracy if the prevalence of high blood drug concentrations was less than 15%. Conclusion: Dividing the drug concentration in oral fluid by the OF/B regression coefficient gave an acceptable estimation of high blood drug concentrations in a population, and may therefore give valuable additional information on possible drug impairment, e. g. in roadside surveys of drugs and driving. If good data on the distribution of OF/B ratios are available, a Monte Carlo simulation may give better accuracy.

Gray TR; Dams R; Choo RE; Jones HE; Huestis MA. Methadone disposition in oral fluid during pharmacotherapy for opioid-dependence. Forensic Science International 206(1-3): 98-102, 2011. (31 refs.)

Introduction: Oral fluid testing is widely used for detecting drug exposure, but data describing methadone and metabolites in oral fluid during pharmacotherapy for opioid-dependence are relatively limited. Methods: 414 oral fluid specimens from 16 opioid-dependent pregnant women receiving daily methadone were analyzed for methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), and methadol by liquid chromatography-mass spectrometry. Results: All oral fluid specimens contained methadone greater than 1 ng/mL; 88% were positive for EDDP and 12% for methadol. Over 95% of oral fluid specimens exceeded the 20 ng/mL methadone cutoff set by the European Driving Under the Influence of Drugs, Alcohol and Medicines (DRUID) study. Methadone and EDDP oral fluid concentrations were highly variable within and between participants, did not predict methadone dose, but were negatively correlated with pH. Conclusion: Methadone was readily identified in oral fluid at concentrations greater than 20 ng/mL following daily 30-110 mg/day methadone pharmacotherapy. As no specimens contained only EDDP or methadol, there was no advantage to including these analytes for identification of methadone exposure. As nearly all oral fluid specimens from methadone-maintained patients exceeded the DRUID guideline, the 20 ng/mL cutoff appears to be sensitive enough to detect daily methadone exposure; however, additional indicators of behavioral and/or motor impairment would be necessary to provide evidence of driving impairment.

Guerrero EG; Cederbaum JA. Adoption and utilization of sexually transmitted infections testing in outpatient substance abuse treatment facilities serving high risk populations in the U.S. International Journal of Drug Policy 22(1): 41-48, 2011. (68 refs.)

Background: Although adoption and utilization of sexually transmitted infection (STI) testing is a cost effective public health intervention, it is inconsistently offered or referred out for by outpatient substance abuse treatment (OSAT) programs where at-risk racial/ethnic and sexual minorities receive services. Methods: We explored the organizational adoption and client utilization of STI testing using a nationally representative sample of OSAT facilities in the U.S. in 2005 (N=566). Data missing at random was imputed and the resulting database was analysed using multivariate Tobit and logistic regressions. Results: The analyses suggest that private non-profit facilities, which are the largest providers of OSAT treatment are less likely than public facilities to offer STI testing or to report adequate client utilization rates. Higher utilization was instead associated with professionally accredited facilities, and with facilities whose majority of clients were Latino/a, reported a history of treatment, stayed in treatment longer, or received case management. Conclusion: While OSAT facilities are poised to be primary intervention points for diagnosis and treatment of STIs, only a segment of these facilities provide this preventive practice or manage to refer clients out. As such, U.S. health care policy should ensure the adoption and comprehensive utilization, particularly among high risk clients, of this cost-effective prevention strategy in OSAT admission protocols.

Hughes RR; Walker GS. Rapid screening for the detection and differentiation of gamma-hydroxybutyrate using ion chromatography. Journal of Forensic Sciences 56(5): 1256-1260, 2011. (36 refs.)

The analysis of gamma-hydroxybutyric acid (GHB) is problematic because it is hygroscopic, it lacks a good UV chromophore, and it undergoes heat-induced cyclization. This paper presents a new method utilizing ion-exchange chromatography (IC) with conductivity detection. The simple sample preparation, rapid analysis time, and inorganic anion detection capabilities are all advantages over the current methods. The detection of inorganic salts (formed during GHB synthesis) gives insight into the synthetic route utilized and can aid in drug seizure comparison. The developed method has a detection limit for GHB anions of 0.57 mg/L and chloride of 0.22 mg/L. A comparison of this technique with a current gas chromatography-mass spectrometry technique is presented, and a t-test found that the two methods' results are not statistically different at the 99.9% confidence level demonstrating the merits of this fast, simple, and informative IC method as a routine screening tool.

Jain RB; Wang RY. Association of caffeine consumption and smoking status with the serum concentrations of polychlorinated biphenyls, dioxins, and furans in the general U.S. population: NHANES 2003-2004. Journal of Toxicology and Environmental Health. Part A: Current Issues 74(18): 1225-1239, 2011. (36 refs.)

Smoking appears to enhance the body's clearance of dioxins and dioxin-like polychlorinated biphenyls (PCB) by inducing CYP1A2 activity based on studies with a limited number of participants. This hypothesis was evaluated by using data from National Health and Nutrition Examination Survey. Specifically, adult participants were identified and the sums of their serum lipid-adjusted concentrations of 12 polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans (PCDD/PCDF) congeners, 33 PCB (total), 26 non-dioxin-like PCB, and 6 mono-ortho (dioxin-like) PCB were determined. In addition to evaluating the association of smoking, the association of caffeine consumption and the interaction between them was evaluated. Data analysis included regression models that were fitted with age, gender, race/ethnicity, and body mass index (BMI). R(2) varied from 34.8 to 66%. Smokers had significantly lower concentrations of total PCDD/PCDF than nonsmokers. New to this study, a siginificant interaction between caffeine consumption and smoking for total PCB was found. When caffeine was consumed less than once a day, smokers had higher concentrations of total PCB than nonsmokers. However, when caffeine was consumed at least once a day, smokers had lower concentrations than nonsmokers. A significant interaction between age and caffeine consumption frequency for each of the PCB groups was also observed. The differences in concentration between younger and older age groups were greater when caffeine was consumed at least once a day than when caffeine was consumed less frequently. Smoking and caffeine consumption need to be considered in the interpretation of human biomonitoring data because they appear to affect the serum concentrations of these chemicals.

Jankovics P; Varadi A; Tolgyesi L; Lohner S; Nemeth-Palotas J; Koszegi-Szalai H. Identification and characterization of the new designer drug 4 '-methylethcathinone (4-MEC) and elaboration of a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) screening method for seven different methcathinone analogs. Forensic Science International 210(1-3): 213-220, 2011. (26 refs.)

A fast and simple LC-MS/MS method was developed for screening mephedrone, butylone, methylenedioxypyrovalerone (MDPV), flephedrone, methylone and methedrone in bulk powder samples. Samples were separated on a reverse phase column using gradient elution with mixtures of water, acetonitrile and formic acid. After optimization a limit of detection of about 2 ng mL (1) was achieved using multiple reaction monitoring (MRM) mode. Total run time was less than 8 min. Typical fragmentation characteristics of the studied compounds are discussed. The method was successfully applied to several unknown bulk powder samples seized by the Hungarian Customs and Finance Guard. One of the samples contained the new designer drug 4'-methylethcathinone (4-MEC), which was identified and characterized by LC-MS/MS, NMR, FT-IR and LC-TOF-MS techniques. The method is also deemed to be applicable for the screening of simple dosage forms such as tablets and capsules.

Javors MA; Hatch JP; Lamb RJ. Sequential combination of self-report, breath carbon monoxide, and saliva cotinine to assess smoking status. Drug and Alcohol Dependence 113(2-3): 242-244, 2011. (13 refs.)

The purpose of this analysis was to develop an algorithm for the cost effective and accurate assessment of smoking during the previous few days by combining self-report, breath carbon monoxide (BCO), and saliva cotinine (SCOT). These measurements are convenient, quantitative, and do not require invasive procedures. The data used to devise the algorithm were gathered during a treatment trial of participants seeking to stop smoking. Self-report of smoking was determined using a written questionnaire, BCO was measured with a handheld breathalyzer, and sCOT was quantified using a high sensitivity ELISA. Participants: were 130 males and 97 females between the ages of 19 and 67 years who reported smoking at least 15 cigarettes a day and had a BCO level >= 15 ppm. Self-reports and BCO levels were collected at each of 6 visits (V0-V5) and sCOT levels were determined at V0 and V5. Based on the data collected, we recommend that the sequential determination of self-reported smoking, BCO level, and sCOT level be employed to assess smoking during the previous few days to minimize the higher cost and longer turnaround time associated with the sCOT test while maximizing accuracy.

Jones AW; Holmgren A. Concentration ratios of free-morphine to free-codeine in femoral blood in heroin-related poisoning deaths. Legal Medicine 13(4): 171-173, 2011. (15 refs.)

The concentrations of free-morphine (Mo), free-codeine (Co) and 6-monoacetyl morphine (6-MAM) were determined in femoral blood in N = 747 heroin-related deaths. The opiates were determined by isotope dilution gas chromatography-mass spectrometry after solid-phase extraction. The median blood concentrations of 6-MAM, free-morphine and free-codeine were 0.01 mg/L, 0.24 mg/L and 0.02 mg/L, respectively. The mean and median Mo/Co concentration ratios were 13.2 and 11.0, respectively with a range from 0.2 to 124. Despite the fact that all victims had taken heroin, there were eight cases (1.1%) with a Mo/Co ratio less than one and 18 cases (2.4%) with a ratio less than two. The free-morphine concentration in blood did not depend on the Mo/Co ratio; median 0.29 mg/L (Mo/Co < 2.0) and median 0.25 mg/L (Mo/Co ratio > 2.0). By contrast, the concentration of free-codeine in blood was highly dependent on the Mo/Co ratio; median 0.75 mg/L (Mo/Co < 1.0) and median 0.30 mg/L (Mo/Co ratio < 2.0). A Mo/Co ratio in post-mortem (PM) femoral blood >1.0 is compelling evidence that the deceased had taken illicit heroin. However, finding a low Mo/Co ratio (<1.0 or <2.0) does not preclude use of heroin because such low ratios are possible if a person had co-ingested heroin along with use or abuse of codeine medication.

Kohler E; Avenarius S; Rabsilber A; Gerloff C; Jorch G. Nicotine and its metabolites in amniotic fluid at birth: Assessment of prenatal tobacco smoke exposure. Human & Experimental Toxicology 29(5): 385-391, 2010. (27 refs.)

Amniotic fluid was collected from 78 pregnant women at birth additionally with their urine prior to delivery as well as neonatal urine and meconium. The smoking markers, nicotine and its metabolites cotinine and trans-3'-hydroxycotinine (OH-cotinine), were determined using high-performance liquid chromatography (HPLC). The self-reported smoking status during pregnancy determined by means of a questionnaire was verified by measurement of maternal urine. In all smokers, nicotine metabolites were detected in amniotic fluid and in 80% of them nicotine as well. However, the sum of the nicotine metabolites (Sum(met)) was significantly lower (p < .001) in amniotic fluid (704 +/- 464 nmol/L) than in meconium (921 +/- 588 nmol/L), neonatal urine (1139 +/- 813 nmol/L) and maternal urine (4496 +/- 3535 nmol/L). Concentrations of nicotine metabolites in amniotic fluid correlated well (p < .001) with that in the other specimen types. After environmental tobacco smoke (ETS) exposure, no nicotine or nicotine metabolites were detectable in amniotic fluid but only in maternal and neonatal urine. Analysis of amniotic fluid at birth lends itself to verifying smoking habits during pregnancy and clearly discriminating from ETS exposure, but it is not a suitable approach to differentiating between ETS exposure and non-exposure.

Kronstrand R; Nystrom I; Forsman M; Kall K. Hair analysis for drugs in driver's license regranting. A Swedish pilot study. Forensic Science International 196(1-3): 55-58, 2010. (21 refs.)

When being convicted for petty drug offence or driving under the influence of drugs in Sweden, the driving license may be suspended. To regain the license, the person has to prove that he or she has been drug free during an observation period. This is controlled by urine samples taken at several occasions. However, the risk of manipulation and the risk of false negative urine samples are high. In addition, many people find it difficult or embarrassing to urinate when observed. Hair sampling might therefore be a welcome option to this procedure, with its easy sampling and minimal risk of manipulation. The longer detection window may also provide better information to the physician. The aim of this work was to evaluate if clients preferred hair samples to urine and to investigate practical and interpretive problems or advantages with hair samples. Ninety-nine hair samples and 198 urine samples were collected from 84 clients during the 12 month study period. Hair samples were divided into either one segment (0-3 cm) or two segments (0-3 and 3-6 cm) depending on the length. The hair samples were screened with LC-MS-MS for 20 drugs and confirmation of positive results were performed with GC-MS or LC-MS-MS. The results were compared to urine samples taken at two occasions during the observation period. To cover the timeframe of the urine samples hair was collected 2 weeks after the second sample. The urine samples were analysed with immunochemical screening and positive results confirmed with GC-MS or LC-MS-MS. Seventy-four clients presented with negative results in both urine and hair. Hair analysis identified illegal drugs at seven different occasions whereas urine failed to identify any illegal drugs. However the thresholds used may still be too high to find sporadic use as clients that admitted to use drugs sporadically presented with drug concentrations lower than the agreed thresholds but above the limit of detection. This implicates that the physician must have an understanding and knowledge of the limitations of the screening methods used. Another important outcome was that the clients approved of hair sampling considering it a better means to prove their drug abstinence. In addition, both the clients and the clinicians thought hair sampling easier than urine sampling. We believe that hair analysis can offer several advantages compared to urine analysis for clinicians working with driving license regranting.

Kulaga V; Shor S; Koren G. Correlation between drugs of abuse and alcohol by hair analysis: Parents at risk for having children with fetal alcohol spectrum disorder. Alcohol 44(7/8, special issue): 615-621, 2010. (63 refs.)

The fatty acid ethyl esters (FAEEs) hair test, a biomarker of excessive alcohol exposure, has demonstrated its potential for use in fetal alcohol spectrum disorder (FASD) diagnosis. FASD may be compounded by polydrug exposure. Our objective was to determine the likelihood of positive FAEE test among parents testing positive for other drugs of abuse. Samples submitted for FAEE hair analysis by Children's Aid Societies between October 2005 and May 2007, also concurrently tested for cocaine, cannabinoids, opiates, methamphetamine, amphetamine, benzodiazepines, methadone, and/or oxycodone, were included in our analysis. Subjects consisted of parents suspected of using excessive amounts of alcohol. Parents testing positive for drugs of abuse had a significantly increased risk for testing positive for high FAEE. Mothers testing positive for heavy chronic alcohol use were found to have a threefold increased risk of testing positive for cocaine (odds ratio = 3.26, 1.1-9.7). Our results suggest that parents abusing stimulants are at risk of high alcohol exposure, which put their unborn children at risk for FASD.

Kuras MJ; Wachowicz MJ. Cannabis profiling based on its elemental composition: Is it possible? Journal of Forensic Sciences 56(5): 1250-1255, 2011. (19 refs.)

Elemental composition of 85 cannabis samples was established using GF AAS and ICP OES methods. The robustness of the method was determined by analyzing eight independently prepared replicates from a single cannabis plant. The accuracy of the method was established by analyzing four plant certified reference material samples. The ability of discriminant analysis using elemental compositions to distinguish between fiber cannabis samples collected from four different regions of Poland was evaluated. Then, a classification model was developed that correctly classified selected samples of known origin. Cannabis samples confiscated by law enforcement agencies have also been subjected to discriminant analysis. A classification model has been developed for four locations in Poland (Bialystok, Koscierzyna, the environs of Skarzysko Kamienna, and Bydgoszcz), to help determine where samples of unknown origin could have been grown.

Lauterbach JH; Bao M; Joza PJ; Rickert WS. Free-base nicotine in tobacco products. Part II. Determination of free-base nicotine in the aqueous extracts of smokeless tobacco products and the relevance of these findings to product design parameters. Regulatory Toxicology and Pharmacology 59(1): 8-18, 2011. (51 refs.)

Reports in the peer-reviewed literature and popular press have alleged that smokeless tobacco product (STP) manufacturers increase the addictiveness of their products by adjusting formulae to increase the relative percentage of nicotine in STP that is not protonated. Such nicotine is more popularly, but incorrectly, known as free-base nicotine ("FBN") as it is a calculated amount as opposed to a real chemical species in the STP. Some regulators have mandated reporting of FBN as estimated by Henderson-Hasselbalch equation ("HHE") using the pH-value of an aqueous suspension (or extract) of SIP. This is technically incorrect because the HHE is only valid in pure dilute aqueous solution of a single base and its conjugate acid. The aqueous suspensions (or extracts) of SIP often contain high concentrations of salts and polymeric anions such as pectate and many other compounds, and there is a molar excess of ammonia over nicotine in some products. These are heretofore-unrecognized sources of error in use of the HHE to estimate relative amount of nicotine that is not protonated results in inaccurate FBN-values. Thus, it is not surprising that attempts to show the relevance of estimated value of FBN in SIP to human physiology have failed.

Lee S; Han E; In S; Choi H; Chung H; Chung KH. Analysis of pubic hair as an alternative specimen to scalp hair: A contamination issue. Forensic Science International 206(1-3): 19-21, 2011. (8 refs.)

Pubic hair is often analyzed as an alternative to scalp hair to prove previous drug use. However, urine is a potential source of external contamination. In the present study, the concentrations of methamphetamine (MA) and amphetamine (AP) in both scalp and pubic hair from illegal MA users were compared. Furthermore, in order to investigate the external contamination of pubic hair by urine, MA and AP absorbed into pubic hair that had been contaminated with authentic urine from a MA user were measured using a previously validated method. The effect of shampoo-wash on the contaminated pubic hair was also examined. However, no correlation was found in the MA and AP concentrations between scalp and pubic hair from illegal MA users. As the number of contamination events by authentic urine increased, the concentrations of MA and AP in pubic hair increased. Both MA and AP were detected in the first methanol washes of the contaminated hair samples but were not detected in the second methanol washes. As the number of shampoo-washes of the contaminated pubic hair increased, the concentrations of MA and AP gradually decreased. Even though pubic hair can be used as an alternative to scalp hair to prove previous drug use, it should be avoided when estimating drug use history. It should be also noted that higher quantitative results in pubic hair do not necessarily represent heavier drug use.

Levin FR; Mariani JJ; Brooks DJ; Xie S; Murray KA. Delta(9)-Tetrahydrocannabivarin testing may not have the sensitivity to detect marijuana use among individuals ingesting dronabinol. Drug and Alcohol Dependence 106(1): 65-68, 2010. (33 refs.)

The purpose of this study was to determine whether Delta(9)-tetrahydrocannabivarin (THCV), a plant cannabinoid, is a sensitive measure to detect recent marijuana use in cannabis dependent patients. It has been purported that smoking an illicit plant cannabis product will result in a positive THCV urinalysis, whereas the oral ingestion of therapeutic THC such as dronabinol will result in a negative THCV urinalysis, allowing for discrimination between pharmaceutical THC products and illicit marijuana products. In a double-blind placebo-controlled trial to determine the efficacy of dronabinol in cannabis dependence, all 117 patients produced a positive urine for the marijuana metabolite 11-nor-Delta(9)-THC-9-carboxylic acid: THC-COOH, but 50% had an undetectable (<1 ng/ml) THCV-COOH test. This suggests that THCV may not be a sensitive enough measure to detect recent marijuana use in all heavy marijuana users or that its absence may not discriminate between illicit marijuana use and oral ingestion of THC products such as dronabinol. We propose that the lack of THCV detection may be due to the variability of available cannabis strains smoked by marijuana users in community settings.

Levy S; Knight JR; Moore T; Weinstein Z; Sherritt L; Weiss RD. Acceptability of drug testing in an outpatient substance abuse program for adolescents. Journal of Adolescent Health 48(3): 229-233, 2011. (23 refs.)

Background: Laboratory drug testing programs may be effective in reducing substance use by adolescents, but developmentally appropriate programs have not been described, and it is unknown if adolescents would be willing to participate in drug testing. Objective: To describe a drug testing protocol for adolescents and report on acceptance rate by patients participating in an outpatient adolescent substance abuse program. Methods: Eligible adolescents participating in an outpatient substance abuse treatment program were offered a random laboratory drug testing program that is described in detail in this manuscript. We recorded whether they accepted and, if not, the reason for refusal. Results: Of the first 114 eligible patients, 67 (59%) agreed to participate in a drug testing program (PDT). Conclusions: A majority of adolescents participating in an outpatient drug treatment program agreed to participate in a drug testing program that requires frequent urine specimens and reports results to parents. Future studies should determine how this program affects treatment outcomes and whether this program is feasible in primary care.

Li LH; Galloway GP; Verotta D; Everhart ET; Baggott MJ; Coyle JR; Lopez JC; Mendelson J. A method to quantify illicit intake of drugs from urine: Methamphetamine. Journal of Pharmacology and Experimental Therapeutics 338(1): 31-36, 2011. (16 refs.)

Qualitative urinalysis can verify abstinence of drug misuse but cannot detect changes in drug intake. For drugs with slow elimination, such as methamphetamine (MA), a single episode of abuse can result in up to 5 days of positive urine drug screens. Thus, interventions that produce substantial decreases in drug use but do not achieve almost complete abstinence are classified as ineffective. Using nonpharmacologic doses of deuterium-labeled /-methamphetamine (/-MA-d(3)) we have developed a simple, robust method that reliably estimates changes in MA intake. Twelve subjects were dosed with 5 mg of /-MA-d(3) daily and challenged with 15, 30, and 45 mg of nonlabeled d-MA (d-MA-d(0)) after reaching plasma steady status of /-MA-d(3). Urinary concentration ratios of d-MA-d(0) to l-MA-d(3) provided clear separation of the administered doses with as little as 15-mg dose increments. Administered doses could not be resolved using d-MA-d(0) concentrations alone. In conclusion, the urinary [d-MA-d(0)]:[/-MA-d(3)] provides a quantitative, continuous measure of illicit MA exposure. The method reliably detects small, clinically relevant changes in illicit MA intake from random urine specimens, is amenable to deployment in clinical trials, and can be used to quantify patterns of MA abuse.

Lopatka M; Vallat M. Surface granularity as a discriminating feature of illicit tablets. Forensic Science International 210(1-3): 188-194, 2011. (19 refs.)

In this paper we propose an innovative methodology for automated profiling of illicit tablets by their surface granularity; a feature previously unexamined for this purpose. We make use of the tiny inconsistencies at the tablet surface, referred to as speckles, to generate a quantitative granularity profile of tablets. Euclidian distance is used as a measurement of (dis) similarity between granularity profiles. The frequency of observed distances is then modelled by kernel density estimation in order to generalize the observations and to calculate likelihood ratios (LRs). The resulting LRs are used to evaluate the potential of granularity profiles to differentiate between same-batch and different-batches tablets. Furthermore, we use the LRs as a similarity metric to refine database queries. We are able to derive reliable LRs within a scope that represent the true evidential value of the granularity feature. These metrics are used to refine candidate hit-lists form a database containing physical features of illicit tablets. We observe improved or identical ranking of candidate tablets in 87.5% of cases when granularity is considered.

Lowry JA. Opiate-positive immunoassay screen in a pediatric patient. (commentary). Clinical Chemistry 56(8): 1224-1225, 2010. (1 refs.)

Mario JR. A probability-based sampling approach for the analysis of drug seizures composed of multiple containers of either cocaine, heroin, or cannabis. Forensic Science International 197(1-3): 105-113, 2010. (33 refs.)

A probability-based analytical sampling approach for seized containers of cocaine, cannabis, or heroin, to answer questions of both content weight and identity, is described. It utilizes the Student's t distribution, and, because of the lack of normality in studied populations, the power of the Central Limit Theorem with samples of size 20 to calculate the mean net weights of multiple item drug seizures. Populations studied ranged between 50 and 1200 units. Identity determination is based on chemical testing and sampling using the hypergeometric distribution fit to a program macro - created by the European Network of Forensic Science Institutes (ENFSI) Drugs Working Group. Formal random item selection is effected through use of an Excel (R)-generated list of random numbers. Included, because of their impact on actual practice, are discussions of admissibility, sufficiency of proof, method validation, and harmony with the guidelines of international standardizing bodies.

McDermott SD; Power JD; Kavanagh P; O'Brien J. The analysis of substituted cathinones. Part 2: An investigation into the phenylacetone based isomers of 4-methylmethcathinone and N-ethylcathinone. Forensic Science International 212(1-3): 13-21, 2011. (10 refs.)

During the analysis of "seized samples'', suspected of containing 4-methylmethcathinone (mephedrone) and N-ethylcathinone (ethcathinone) additional compounds were observed in the GCMS chromatogram. These compounds were suspected to be the corresponding phenylacetone isomers of mephedrone and ethcathinone respectively. These isomers are referred to as iso-mephedrone and iso-ethcathinone, respectively. The identity of these compounds was verified by synthesising the isomers from known starting materials and comparing them with the compounds found in the seized samples. Analytical data, GCMS, NMR and IR on these compounds are provided. Possible explanations for the presence of these compounds in the seized samples are explored. Contaminated starting material is one suggestion. Rearrangement of the propiophenone based product to the phenylacetone based product is also suggested. The reaction of the alpha-bromopropiophenone with a primary amine can also lead to the phenylacetone based product. The presence of these isomeric compounds in seized samples could be used to compare different samples and attempt to establish a common origin.

McDonell MG; Angelo F; Sugar A; Rainey C; Srebnik D; Roll J et al. A pilot study of the accuracy of onsite immunoassay urinalysis of illicit drug use in seriously mentally ill outpatients. American Journal of Drug and Alcohol Abuse 37(2): 137-140, 2011. (12 refs.)

Objectives: This pilot study investigated the accuracy of onsite immunoassay urinalysis of illicit drug use in 42 outpatients with co-occurring substance use disorders and serious mental illness. Methods: Up to 40 urine samples were submitted by each participant as part of a larger study investigating the efficacy of contingency management in persons with co-occurring disorders. Each sample was analyzed for the presence of amphetamine, methamphetamine, cocaine, marijuana, and opiates or their metabolites using onsite qualitative immunoassays. One onsite urinalysis was randomly selected from each participant for confirmatory gas chromatography--mass spectrometry (GC--MS) analyses. Results: Agreement between immunoassay and GC--MS was calculated. Agreement was high, with 98%% agreement for amphetamine, methamphetamine, opiate, and marijuana. Agreement for cocaine was 93%. Conclusions: Results of this pilot study support the use of onsite immunoassay screening cups as an assessment and outcome measure in adults with serious mental illness. Scientific significance: Data suggest that onsite urinalysis screenings may be a helpful assessment tool for measuring clinical and research outcomes.

Meng PJ; Wang YY. Small volume liquid extraction of amphetamines in saliva. Forensic Science International 197(1-3): 80-84, 2010. (8 refs.)

present study introduced a procedure of small volume liquid extraction of amphetamines, including amphetamine (AM); methamphetamine (MA); 3,4-methylenedioxyamphetamine (MDA); 3,4-methylenemethamphtamine (MDMA), in saliva. Extraction efficiencies were compared between the conventional volume liquid phase extraction (LPE) and the small volume one, in which <100 mu L solvent was used instead of several milliliters in LPE. Conditions such as types and volumes of organic solvent used in the extraction and concentrations of target analytes in aqueous samples were examined. Results showed that small volume liquid extraction had an enrichment effect on the analytes. After extraction, the organic phase was either directly drawn out for GC analysis, or partially transferred to another vial for derivatization. Detection limits were less than 5 ng/mL in saliva using GC/MS-SIM after derivatization. RSD (of peak area ratios) was less than 15% at all drug concentrations. The method was used in the analyses of saliva collected from amphetamine abusers, and was proven to be practical for detecting trace amounts of amphetamines in saliva.

Mieczkowski T. Assessing the potential for racial bias in hair analysis for cocaine: Examining the relative risk of positive outcomes when comparing urine samples to hair samples. Forensic Science International 206(1-3): 29-34, 2011. (36 refs.)

This article examines the conjecture that hair analysis, performed to detect cocaine use or exposure, is biased against African Americans. It does so by comparing the outcomes of 33,928 hair and 105,792 urine samples collected from both African American and white subjects. In making this comparison the analysis seeks to determine if there is a departure in rates of positive and negative outcomes when comparing the results of hair analysis for cocaine to the results from urinalysis for cocaine by racial group. It treats urine as an unbiased test. It compares both the relative ratios of positive outcomes when comparing the two groups and it calculates the relative risk of outcomes for each group for having positive or negative outcomes. The findings show that the ratios of each racial group are effectively same for hair and urine assays, and they also show that the relative risk and risk estimates for positive and negative outcomes are the same for both racial groups. Considering all samples, the cocaine positive risk estimate for the hair samples comparing the two racial groups is 3.28 and for urinalysis the risk estimate is 3.10 (Breslow-Day chi(2).250, 1 df, p = 0.617) a non-significant difference in risk. For pre-employment samples, the cocaine positive risk estimate for the hair samples comparing the two racial groups is 3.10 and for urinalysis the risk estimate is 2.90 (Breslow-Day chi(2).281, df = 1, p = 0.595), also a non-significant difference in risk.

Moore C. Oral fluid and hair in workplace drug testing programs: new technology for immunoassays. Drug Testing and Analysis 3(3): 166-168, 2011. (5 refs.)

Workplace drug testing programs have embraced both oral fluid and hair as testing matrices. Saliva is popular due to its easy, rapid collection; its non-invasiveness compared to urine or blood; the convenience of collecting a specimen anywhere, anytime; and the difficulty of adulteration. The main advantage of saliva, however, remains its suitability for post-accident or 'for-cause' testing since the presence of a drug can assist in the determination of an individual being 'under the influence' of a drug. Hair, on the other hand, is useful for workplace programs, since its ability to provide historical information on drug intake ensures it is an excellent specimen for pre-employment testing. Both technologies have enjoyed collection and laboratory improvements for immunoassay screening over the last few years, and these are discussed in this perspective.

Mordal J; Holm B; Gossop M; Romoren M; Morland J; Bramness JG. Psychoactive substance use among patients admitted to an acute psychiatric ward: Laboratory findings and associations with clinical characteristics. Nordic Journal of Psychiatry 65(3): 208- 215, 2011. (33 refs.)

Background: Estimates of psychoactive substance use among acutely admitted psychiatric patients vary among studies, and few have used comprehensive laboratory methods. Aims: This study used chromatography-based analyses of blood and urine to identify the rates of substance use among acute psychiatric admissions, and to study the associations with socio-demographic variables, clinical characteristics and patients'' reports of symptoms, substance use and need for treatment. Methods: A cross-sectional study was conducted in 2006/2007 in Oslo, Norway. Blood and urine samples were collected from 298 acute psychiatric admissions and extensively analysed for alcohol, medicinal and illicit drugs. Psychotic symptoms were assessed with the positive subscale of the Positive and Negative Syndrome Scale. Patient self-report questionnaires included the Alcohol and Drug Use Disorder Identification Tests. Patients were also asked if they needed professional help for substance use. Results: Psychoactive substances were detected in 63% of the 298 admissions, medicinal drugs in 46%, alcohol in 12% and illicit drugs in 28%. Patients using alcohol had a high suicidal risk score at admission and the shortest length of stay (median 1 day). Use of illicit drugs was associated with psychotic symptoms and readmission. Self-report questionnaires indicated harmful use of alcohol for half of the patients and of other substances for one-third. A need for professional help for substance use was reported by one-third of patients. Conclusion: Given the high rates of substance use and the important clinical associations, drug screening seems warranted in acute psychiatric settings. Interventions designed for substance-using patients should be developed and integrated.Copyright 2011, Informa Healthcare

Mordal J; Holm B; Morland J; Bramness JG. Recent substance intake among patients admitted to acute psychiatric wards: Physician's assessment and on-site urine testing compared with comprehensive laboratory analyses. Journal of Clinical Psychopharmacology 30(4): 455-459, 2010. (21 refs.)

This cross-sectional study of acute psychiatric admissions compared physicians' assessments of recent substance intake and on-site urine testing with comprehensive laboratory drug analyses. The sample comprised 325 consecutive admissions from 2 acute psychiatric wards. Physicians on call were asked to judge if the patient had recently taken benzodiazepines, opiates, alcohol, amphetamines, cannabis, or cocaine. Blood and urine samples were obtained and analyzed with chromatographic laboratory methods for a wide range of substances. A routine on-site urine screening test was performed in 92 of the cases. Physicians' assessments and on-site urine testing were compared with the reference standard of laboratory analyses. The sensitivity of the physician's assessment was highest for amphetamines (76%), followed by benzodiazepines (61%), opiates (57%), cannabis (55%), and cocaine (50%), whereas specificity was greater than 90% for all substances. The sensitivity of the on-site test ranged from 76% for amphetamine to 97% for cannabis, and specificity ranged from 82% for cannabis to 100% for cocaine. The study indicates clinical underdetection of recent substance intake among acute psychiatric admissions. On-site urine testing identified substance use that was not recognized by the physician's initial assessment, although specificity for cannabis and benzodiazepines was low. Chromatographic methods, which offered important supplementary information about substance use, should be considered for the routine screening of acutely admitted psychiatric patients.

Nesmerak K; Sticha M; Cvancarova M. HPLC/MS analysis of historical pharmaceutical preparations of heroin and cocaine. Analytical Letters 43(16): 2572-2581, 2010. (24 refs.)

Pharmaceutical preparations of heroin and cocaine more than seventy years old were analyzed using RP-HPLC. The composition of mobile phase was optimized. The components were identified by MS2 or MS3, and the APPI fragmentation mechanisms of compounds found were proposed. The sample of heroin hydrochloride injection solution consists of 96.1% morphine and 3.9% of codeine. The sample of cocaine hydrochloride injection solution consists of 26.9% cocaine, 31.5% benzoylecgonine, 17.4% ecgonine, and 24.2% ecgonine methyl ester.

Oechsler S; Skopp G. Buprenorphine and major metabolites in blood specimens collected for drug analysis in law enforcement purposes. Forensic Science International 195(1-3): 73-77, 2010. (22 refs.)

A liquid chromatographic/electrospray ionization tandem mass spectrometric method for the quantification of buprenorphine (BUP), norbuprenorphine (NBUP), buprenorphine-3-beta-D-glucuronide (BUPG) and norbuprenorphine-3-beta-D-glucuronide (NBUPG) in serum samples was developed and validated. Pre-treatment of BUP and NBUP was by liquid-liquid extraction, while glucuronides were favourably isolated by solid phase extraction. Separation in 2 separate runs (2 x 5 min) was achieved using isocratic elution. The method was applied to 20 authentic serum specimens collected for law enforcement purposes where BUP intake had been indicated. The parent drug was not detectable in half of the specimens at a lower limit of detection of 0.2 ng/mL, whereas NBUP could be determined from any sample but one. NBUPG is the majormetabolite present, which could be identified along with BUPG in all samples under investigation. In authentic specimens it could be advisable to monitor BUP metabolites along with the parent drug.

Onuegbu AJ; Olisekodiaka JM; Adebolu OE; Adesiyan A; Ayodele OE. Coffee consumption could affect the activity of some liver enzymes and other biochemical parameters in healthy drinkers. Medical Principles and Practice 20(6): 514-518, 2011. (30 refs.)

Objective: To investigate the effect of coffee consumption on some liver function indices in adult male and female Nigerians. Subjects and Methods: Thirty apparently healthy subjects, consisting of 18 men and 12 women, were made to consume 2 g of coffee daily for a total of 30 days. Activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and plasma concentrations of total and conjugated bilirubin, total protein and albumin were determined using standard methods. Results: Relative to baseline values, coffee consumption raised mean levels of ALT by 4 IU/l (p < 0.001), AST by 2.0 1 U/l (p < 0.001), ALP by 3.0 1 U/l (p < 0.01), total bilirubin by 0.90 mg/dl (p < 0.05) and total protein by 1.1 g/l (p < 0.05). Gender differences were observed. Significantly higher mean ALP concentration was only seen in male subjects, while mean bilirubin concentration was significantly raised in female volunteers alone. On the other hand, the mean total protein and albumin concentrations in individual male and female groups were not significantly altered (p > 0.05 in each case). Conclusion: The result obtained from the study suggests that short-term consumption of coffee might have a significant effect on the integrity of the liver function tests studied.

Perera V; Gross AS; Xu HM; McLachlan AJ. Pharmacokinetics of caffeine in plasma and saliva, and the influence of caffeine abstinence on CYP1A2 metrics. Journal of Pharmacy and Pharmacology 63(9): 1161-1168, 2011. (50 refs.)

Objectives: To investigate the utility of metrics of CYP1A2 activity using caffeine as a probe, and saliva and plasma sampling with or without a 24-h caffeine abstinence. Methods This was a cross-over pharmacokinetic study in 30 healthy male subjects who received a single oral 100 mg caffeine dose after 24-h caffeine abstinence or after maintaining their regular caffeine intake (no caffeine abstinence). Serial blood and saliva samples were collected simultaneously over 24 h. Caffeine and paraxanthine concentrations were measured using a validated HPLC assay. Key findings There was a strong correlation between the paraxanthine/caffeine AUC(0-24) ratio (reference metric) and the paraxanthine/caffeine concentration (C(t)) ratio at 4 h (C(4)) in both saliva and plasma (r >= 0.75). The paraxanthine/caffeine AUC(0-24) ratio in plasma and saliva did not differ between the 24-h caffeine abstinence and the no abstinence period (P > 0.05). The optimal paraxanthine/caffeine C(t) that correlated with the plasma paraxanthine/caffeine AUC(0-24) ratio in the 24-h abstinence period was 2 and 4 h (r = 0.88) in plasma, and 4 and 6 h in saliva (r = 0.70), while it was the saliva 4 h time-point in the no abstinence period (r = 0.78). Conclusions: The saliva paraxanthine/caffeine concentration ratio at 4 h was a suitable metric to assess CYP1A2 activity after oral administration of caffeine without the need for 24-h caffeine abstinence.

Piper T; Geyer H; Schanzer W. Degradation of urine samples and its influence on the C-13/C-12 ratios of excreted steroids. Drug Testing and Analysis 2(11-12, special issue): 620-629, 2010. (29 refs.)

The degradation processes in deficiently stored urine samples are well investigated regarding steroid concentrations and diagnostic ratios, such as the quotient of testosterone divided by epitestosterone. In contrast, nothing is known about the influence on carbon isotope ratios (CIR) by inappropriate storage conditions. In general, it is assumed that degradation, i.e. deconjugation or dehydrogenation, does not change CIR and thus CIR can be used in cases where the steroid profile turns out to be invalid. Therefore, the CIR of urinary steroids was investigated in different urine samples during the course of degradation over a time period of six months. Several steroids excreted as glucuronides (androsterone (A), etiocholanolone (E), testosterone, pregnanediol (PD) and 5 alpha- and 5 beta-androstane-3 alpha,17 beta-diol) or sulfo-conjugated (A, E and androst-5-ene-3 beta,17 beta-diol (5EN17b)) were investigated together with their unconjugated correspondents (A, E, PD and 5EN17b) and the main dehydrogenation products (5a- and 5 beta-androstane-3,17-diol and androst-4-ene-3,17-diol). For this purpose, the exiting methods for CIR determination were extended and validated. In addition, the urinary concentrations of all investigated steroids were monitored. Particular attention was paid to dehydroepiandrosterone conjugated and unconjugated together with its degradation product 3 alpha,5-cyclo-5 alpha-androstan-6 beta-ol-17-one as here the strongest influence on CIR was expected.

Porter WH. Opiate-positive immunoassay screen in a pediatric patient. (commentary). Clinical Chemistry 56(8): 1223-1224, 2010. (0 refs.)

Purkis SW; Troude V; Duputie G; Tessier C. Limitations in the characterisation of cigarette products using different machine smoking regimes. Regulatory Toxicology and Pharmacology 58(3): 501-515, 2010. (40 refs.)

It is recognised that no single machine smoking regime can represent the different behaviours of individual human smokers. It has been argued that the current ISO standard regime provides machine yields that are somewhat low for certain cigarette designs compared to human intake. Various cigarette machine smoking regimes have been proposed as options for regulatory use to provide data that reflect "average" or "maximum" yields as related to human intake. Some public health representatives have proposed that the intense regime mandated for testing in Canada with 100% of the ventilation holes in the cigarette filter blocked, should be used for product characterisation and that it is not necessary that it should reflect general human smoking behaviour. We believe that this is a flawed approach because our studies and those of other workers demonstrate that the conditions generated in the cigarette when using this intense machine smoking regime are extreme in comparison to the conditions found for regimes based more realistically on human smoking. In this paper, we provide data to show that smokers modify their smoking intensity over the course of smoking in response to changes in draw resistance, smoke concentrations and smoke temperatures. We compare changes in and interactions between these parameters during puffing when smoking cigarettes of different designs. Cigarettes were smoked using various machine smoking regimes previously proposed for smoke testing as well as a regime based on human smoking data from an 'in-house' study. Puffing parameters were derived from this study to represent the 'average smoker' under laboratory conditions and equivalent to the 90th percentile when the studied smokers smoked under natural conditions. Biomarker data from human uptake studies have shown that ventilation is an effective cigarette design tool to reduce total smoke constituent uptake in humans so demonstrating that any blocking of filter ventilation is far from 100%. Likewise, this current work also shows how smokers modify their smoking behaviour in ways not well reflected by the 100% ventilation blocking regime. It seems logical that any machine smoking regime chosen for future product regulation should reflect these findings for it to have valid public health relevance. In addition, it seems misguided to discourage product design features, such as ventilation, which clearly can provide products with reduced human smoke exposure, just to maintain the dogma, counter to the scientific evidence, that there must be a regulatory regime with 100% ventilation blocking.

Rana V; Canamares MV; Kubic T; Leona M; Lombardi JR. Surface-enhanced Raman spectroscopy for trace identification of controlled substances: Morphine, codeine, and hydrocodone. Journal of Forensic Sciences 56(1): 200-207, 2011. (27 refs.)

We obtain the normal Raman and surface-enhanced Raman spectrum of three controlled substances: morphine, codeine, and hydrocodone. The spectra are assigned with the aid of density functional theory. Because of rather intense fluorescence, normal Raman spectra suffer from poor signal-to-noise, even when differential subtraction techniques are employed. On the other hand, surface enhancement by Ag nanoparticles both enhances the Raman signal and suppresses the fluorescence, enabling far more sensitive detection and identification. We also present a set of discriminant bands, useful for distinguishing the three compounds, despite the similarities in their structures.

Samms WC; Jiang YJ; Dixon MD; Houck SS; Mozayani A. Analysis of alprazolam by DART-TOF mass spectrometry in counterfeit and routine drug identification cases. Journal of Forensic Sciences 56(4): 993-998, 2011. (14 refs.)

The high prevalence of alprazolam abuse translates to an increased workload for crime laboratories in characterizing seized tablets. These tablets may originate as diverted pharmaceuticals or counterfeited mimics, so efficient analytical techniques should provide confirmatory data while minimizing destruction of evidence. We offer the first report of a validated forensic method for confirming alprazolam tablets by direct analysis in real time-time of flight (DART-TOF) mass spectrometric analysis. This technique provides rapid identification of target analytes with minimal sample preparation, allowing direct analysis in the atmospheric sample gap. Selectivity is achieved through high resolution and mass accuracy, unique ion fragments, and chlorine isotopic ratios. This method utilizes fragmentation in two separate voltage functions to observe the alprazolam pseudo molecular ion at 309.09070 using 40 V and major ion fragments of 281.07197 and 205.07657 at 120 V. These parameters allow our laboratory to confirm alprazolam tablets efficiently, without compromising quality forensic standards.

Santali EY; Cadogan AK; Daeid NN; Savage KA; Sutcliffe OB. Synthesis, full chemical characterisation and development of validated methods for the quantification of (+/-)-4 '-methylmethcathinone (mephedrone): A new "legal high". Journal of Pharmaceutical and Biomedical Analysis 56(2): 246-255, 2011. (23 refs.)

The recent global increase in the abuse of 4'-methylmethcathinone and related compounds has developed a requirement for full chemical characterisation of these products. In this work we present full synthetic and chemical characterisation data and supplemental information for mephedrone synthesised as both the hydrobromide and hydrochloride salt. Additionally we report the first fully validated chromatographic methods for the detection and quantitative analysis of the substance both in its pure form and in the presence of a number of common adulterants used in illicit drug manufacture.

Schwilke EW; Gullberg RG; Darwin WD; Chiang CN; Cadet JL; Gorelick DA et al. Differentiating new cannabis use from residual urinary cannabinoid excretion in chronic, daily cannabis users. Addiction 106(3): 499-506, 2011. (18 refs.)

Aims: To develop and validate empirically a mathematical model for identifying new cannabis use in chronic, daily cannabis smokers. Design: Models were based on urinary creatinine-normalized (CN) cannabinoid excretion in chronic cannabis smokers. Setting: For model development, participants resided on a secure research unit for 30 days. For model validation, participants were abstinent with daily observed urine specimens for 28 days. Participants: A total of 48 (model development) and 67 (model validation) daily cannabis smokers were recruited. Measurements: All voided urine was collected and analyzed for 11-nor-9-carboxy-Delta 9-tetrahydrocannabinol (THCCOOH) by gas chromatography-mass spectrometry (GCMS; limit of quantification 2.5 ng/ml) and creatinine (mg/ml). Urine THCCOOH was normalized to creatinine, yielding ng/mg CN-THCCOOH concentrations. Urine concentration ratios were determined from 123 513 specimen pairs collected 2-30 days apart. Findings: A mono-exponential model (with two parameters, initial urine specimen CN-THCCOOH concentration and time between specimens), based on the Marquardt-Levenberg algorithm, provided a reasonable data fit. Prediction intervals with varying probability levels (80, 90, 95, 99%) provide upper ratio limits for each urine specimen pair. Ratios above these limits suggest cannabis re-use. Disproportionate numbers of ratios were higher than expected for some participants, prompting development of two additional rules that avoid misidentification of re-use in participants with unusual CN-THCCOOH excretion patterns. Conclusions: For the first time, a validated model is available to aid in the differentiation of new cannabis use from residual creatinine-normalized 11-nor-9-carboxy-Delta 9-tetrahydrocannabinol (CN-THCCOOH) excretion in chronic, daily cannabis users. These models are valuable for clinicians, toxicologists and drug treatment staff and work-place, military and criminal justice drug-testing programs.

Sciotti MA; Hasan L; Scholer A; Jermann TM; Weber JM; Gygax D. Development and characterization of an enzymatic method for the rapid determination of gamma hydroxybutyric acid. Chimia 64(11): 793-798, 2010. (29 refs.)

Gamma hydroxybutyric acid (GHB) is a regulated therapeutic drug, which naturally occurs in mammalian brain tissues as an intermediate of the GABA (gamma aminobutyric acid) neurotransmitter metabolism The increasing misuse of GHB as a narcotic or abusing drug in recent years calls for the development of a simple and rapid screening method as an alternative to the currently available, technically demanding diagnostic methods We have developed a rapid enzymatic assay based on the GHB dehydrogenase of Ralstonia eutropha The enzyme is expressed as a recombinant protein in Escherichia coli and characterized in terms of reaction mechanism and kinetic parameters for the catalysis of conversion of GHB into succinic semialdehyde (SSA) The concomitant NADH production enables spectrophotometric monitoring of the reaction and the quantification of GHB in physiological fluids depending on initial velocities We have tested a panel of twelve serum and urine samples containing GHB concentrations from 0 0 to 2 1 mmol/L GHB dehydrogenase activity obeys a non classical bi bi ping pong mechanism exhibiting substrate inhibition by NAD(+) With an optimal NAD(+) concentration of 3 7 mmol/L in the reaction, the enzyme yields a K-M of 1 0 mmol/L for GHB and a V-max of 3 37 mmol/min/mg The assay shows a linear standard curve from 0 1 to at least 1 mmol/L of GHB Spiking experiments result in mean recoveries of 92% for urine and 114% for serum, respectively The comparison to an ion chromatographic reference method exhibits a mean difference of 10% divergence from the target values in urine and 9% in serum, respectively

Shafiq Q; Mutgi A. Urine opiate screening: False-positive result with levofloxacin. (editorial). Canadian Medical Association Journal 182(15): 1644-1645, 2010. (5 refs.)

Sims M; Tomkins S; Judge K; Taylor G; Jarvis MJ; Gilmore A. Trends in and predictors of second-hand smoke exposure indexed by cotinine in children in England from 1996 to 2006. Addiction 105(3): 543-553, 2010. (30 refs.)

Aims: To explore trends in and predictors of second-hand smoke (SHS) exposure in children. To identify whether inequalities in SHS exposure are changing over time. Design: Repeated cross-sectional study with data from eight annual surveys conducted over an 11-year period from 1996 to 2006. Setting: England. Participants: Nationally representative samples of children aged 4-15 years living in private households. Measurements: Saliva cotinine (4-15-year-olds), current smoking status (8-15-year-olds), smoking status of parents and carers, smoking in the home, socio-demographic variables. Findings: The most important predictors of SHS exposure were modifiable factors-whether people smoke in the house on most days, whether the parents smoke and whether the children are looked after by carers who smoke. Children from more deprived households were more exposed and this remained the case even after parental smoking status has been controlled for. Exposure over time has fallen markedly among children (59% decline over 11 years in geometric mean cotinine), with the most marked decline observed in the period immediately preceding smoke-free legislation. Declines in exposure have generally been greater in children most exposed at the outset. For example, in children whose parents both smoke, median cotinine declined annually by 0.115 ng/ml compared with 0.019 ng/ml where neither parent smokes (P < 0.05). Conclusions: In the 11 years leading up to smoke-free legislation in England, the overall level of SHS exposure in children as well as absolute inequalities in exposure have been declining. Further efforts to encourage parents and carers to quit and to avoid smoking in the home would benefit child health.

Spata J; Kelsberg G; Safranek S. Does office spirometry improve quit rates in smokers? (editorial). Journal of Family Practice 59(10): 593-594, 2010. (7 refs.)

Stefanidou M; Athanaselis S; Spiliopoulou C; Dona A; Maravelias C. Biomarkers of opiate use. (review). International Journal of Clinical Practice 64(12): 1712-1718, 2010. (59 refs.)

The interpretation of toxicological findings is critical for the thorough investigation of the use and abuse of psychoactive substances. A positive analytical result for a sample taken could usually result in criminal proceedings and a punitive outcome for the defendant whose sample was analysed. The detection of markers of illicit opiate misuse is important both in the management of substance misuse and in the postmortem identification of illicit opiate use. The aim of this study was to emphasise the role of opiate biomarkers available at the laboratory and in the clinical environment. Urine remains the biological tool of choice for qualitative detection of illicit drug use in a clinical setting, while quantitative accuracy remains strictly the domain of blood. Accurate interpretation of the screening tests within a clinical setting alongside other relevant information remains the key to the usefulness of any test. Moreover, the finding of a morphine/codeine concentration ratio in blood exceeding unity is a strong evidence that the person had used heroin, as opposed to having taken a prescription analgesic drug containing codeine.

Talio MC; Luconi MO; Masi AN; Fernandez LP. Cadmium monitoring in saliva and urine as indicator of smoking addiction. Science of the Total Environment 408(16): 3125-3132, 2010. (24 refs.)

Cadmium is one of the many substances that may be acquired through active and passive smoking of tobacco. Saliva and urine are proposed for cadmium monitoring of non-smokers, second hand smokers, smokers and tobacco chewing appertaining to San Luis citizens without occupational exposition. Biological samples were collected by the same subjects, under strict proceeding instructions of sampling. Physical characteristics of samples were observed and checked with commercial test. Samples were analyzed using an adapted molecular fluorescence methodology with a previous extraction step. Stability of biological samples was daily studied for a period of one month. The method was successfully validated for accuracy, precision, linearity, specificity, and sensitivity. The simplicity and low coefficient of variance confirm the suitability of the method for urinary and salivary cadmium analyses. On the other side, the obtained results are in concordance with previous national epidemiological dates.

Thevis M; Kuuranne T; Geyer H; Schanzer W. Annual banned-substance review: Analytical approaches in human sports drug testing. (review). Drug Testing and Analysis 3(1): 1-14, 2011. (122 refs.)

The timely update of the list of prohibited substances and methods of doping (as issued by the World Anti-Doping Agency) is an essential aspect of international anti-doping efforts and represents consensual agreement by expert panels regarding substances and the methods of performance manipulation in sports. The annual banned-substance review for human doping controls critically summarizes recent innovations in analytical approaches; its purpose is to improve the quality of doping controls by reporting emerging and advancing methods that focus on detecting known and recently outlawed substances. This review surveys new and/or enhanced procedures and techniques of doping analysis together with information relevant to doping control that has been published in the literature between October 2009 and September 2010.

Uddin M; Maskrey V; Holland R. A study to validate a self-reported version of the ONS drug dependence questionnaire. Journal of Substance Use 16(4): 273-281, 2011. (15 refs.)

Aim: A prospective study to establish the reliability of a self-completion version of the Office for National Statistics (ONS) questionnaire for assessing drug dependence of substance misuse clients. Method: A total of 47 treatment seeking opioid-dependent clients completed the self-complete version of the ONS questionnaire (ONS-sc) followed by the interviewer-administered ONS questionnaire (ONS-ia) at a single clinic appointment. Scores for four Class A drugs (heroin, methadone, speed and crack/cocaine) from both formats were compared. Results: The observed agreement was 87% or more and Cohen's kappa was 0.7 (p < 0.001) or more for all four Class A drugs. Sensitivity for each Class A drugs was 56% or higher and specificity was 87% or higher. Sensitivity for severe heroin dependency was 98% (CI 89-100%). There was a 100% correlation between the ONS-sc and positive urine analysis for heroin use. However, methadone and crack/cocaine drug use appeared under reported. Conclusion: ONS-sc is a feasible, practical and time-saving alternative to a detailed interview on drug dependence. Further research with a larger sample size and non-opiate-dependent clients are needed, as this could prove a useful tool for monitoring clients in everyday practice, or for survey purposes where interviews are impractical.

Van Renterghem P; Van Eenoo P; Sottas PE; Saugy M; Delbeke F. Subject-based steroid profiling and the determination of novel biomarkers for DHT and DHEA misuse in sports. Drug Testing and Analysis 2(11-12, special issue): 582-588, 2010. (39 refs.)

Doping with natural steroids can be detected by evaluating the urinary concentrations and ratios of several endogenous steroids. Since these biomarkers of steroid doping are known to present large inter-individual variations, monitoring of individual steroid profiles over time allows switching from population-based towards subject-based reference ranges for improved detection. In an Athlete Biological Passport (ABP), biomarkers data are collated throughout the athlete's sporting career and individual thresholds defined adaptively. For now, this approach has been validated on a limited number of markers of steroid doping, such as the testosterone (T) over epitestosterone (E) ratio to detect T misuse in athletes. Additional markers are required for other endogenous steroids like dihydrotestosterone (DHT) and dehydroepiandrosterone (DHEA). By combining comprehensive steroid profiles composed of 24 steroid concentrations with Bayesian inference techniques for longitudinal profiling, a selection was made for the detection of DHT and DHEA misuse. The biomarkers found were rated according to relative response, parameter stability, discriminative power, and maximal detection time. This analysis revealed DHT/E, DHT/5 beta-androstane-3 alpha,17 beta-diol and 5 alpha-androstane-3 alpha,17 beta-diol/5 beta-androstane-3 alpha,17 beta-diol as best biomarkers for DHT administration and DHEA/E, 16 alpha-hydroxydehydroepiandrosterone/E, 7 beta-hydroxydehydroepiandrosterone/E and 5 beta-androstane-3 alpha,17 beta-diol/5 alpha-androstane-3 alpha,17 beta-diol for DHEA. The selected biomarkers were found suitable for individual referencing. A drastic overall increase in sensitivity was obtained. The use of multiple markers as formalized in an Athlete Steroidal Passport (ASP) can provide firm evidence of doping with endogenous steroids.

Villain M; Muller JF; Kintz P. Heroin markers in hair of a narcotic police officer: Active or passive exposure? Forensic Science International 196(1-3): 128-129, 2010. (11 refs.)

On March 2007, a police officer (46-year-old man) and a clerk (37-year-old woman) were arrested and subjected to investigation on the charges of drugs of abuse trafficking. The couple was exploiting their administrative positions to make money with the resale of seized drugs. The laboratory was requested to analyse their hair for drugs of abuse. Hair of the 2 subjects tested positive for heroin by GC-MS. A few days later, analysis of hair obtained from 11 other police officers of the same unit was requested, in order to compare the results, as external contamination was proposed to account for the positive results. The aim of the investigations was to demonstrate that passive contamination could not occur for persons dealing every day with drugs of abuse with minimal caution and hygiene, and that the measured concentrations in the arrested subjects correspond to personal abuse. All the narcotic team tested negative, irrespective of the compound.

Wood DM; Davies S; Greene SL; Button J; Holt DW; Ramsey J et al. Case series of individuals with analytically confirmed acute mephedrone toxicity. Clinical Toxicology 48(9): 924-927, 2010. (13 refs.)

Context. Previous reports of acute toxicity/harm associated with mephedrone use have been based on self-reported mephedrone use; toxicological screening has not been undertaken in these cases to determine whether mephedrone has been used. Objective. To report the first case series of analytically confirmed mephedrone-related acute toxicity. Materials and methods. Serum samples were collected from individuals presenting to an emergency department (ED) with acute toxicity related to self-reported mephedrone use. Toxicological analysis, by gas-chromatography coupled with mass-spectrometry and liquid chromatography with tandem mass-spectrometry was performed to qualitatively confirm mephedrone use. Symptoms/signs of acute mephedrone toxicity and basic physiological parameters were extracted from the routine ED records. Results. Acute mephedrone-related toxicity was analytically confirmed in seven male patients; the mean +/- SD age was 24.6 +/- 6.5 years (range 16-36 years). Agitation (four patients) was the most common symptom/sign reported; other common symptoms/signs included: palpitations (two patients); chest pain (two patients); self-limiting pre-hospital seizures (one patient) and headaches (one patient). The mean heart rate was 109.1 +/- 21.8 (range 80-140) beats per minute; one patient had a "severe" tachycardia (heart rate of >= 140 bpm). The mean systolic blood pressure was 153.0 +/- 39.6 (range 110-210) mmHg; three patients had clinically significant hypertension (systolic blood pressure >= 160 mmHg). Discussion. These analytically confirmed acute mephedrone toxicity presentations had clinical features of toxicity consistent with an acute sympathomimetic toxidrome (e.g. hypertension, tachycardia and agitation). These findings are similar to the pattern of toxicity seen with other sympathomimetic recreational drugs such as 3,4-Methylenedioxymethamphetamine (MDMA) and cocaine. Conclusion. The process for determining whether a novel psychoactive substance should be controlled often relies on demonstrated/proven acute harm associated with its use. It is important that clinical toxicologists undertake appropriate biological sampling and toxicological analyses in suspected cases of "novel psychoactive drug" toxicity. This will ensure that both clinicians and legislative authorities are informed of the confirmed pattern of toxicity associated with these drugs.

Wurst FM; Thon N; Yegles M; Halter C; Weinmann W; Laskowska B et al. Optimizing heroin-assisted treatment: Assessment of the contribution of direct ethanol metabolites in identifying hazardous and harmful alcohol use. Drug and Alcohol Dependence 115(1-2): 57- 61, 2011. (40 refs.)

Background: Heavy alcohol consumption may accelerate the progression of hepatitis C-related liver disease and/or limit efforts at antiviral treatment in opioid-dependent patients receiving heroin-assisted treatment (HAT). Our study aims to assess alcohol intake among HAT patients by self-reports compared to direct ethanol metabolites. Method: Fifty-four patients in HAT were recruited from the centre for HAT at the University of Basel, Switzerland. The patients completed the Alcohol Use Disorder Identification Test (AUDIT), a self-report questionnaire on past-week ethanol intake and provided samples for the determination of ethyl glucuronide (UEtG) and ethyl sulphate (UEtS) in urine and of ethyl glucuronide (HEtG) in hair. Results: Eighteen patients scored above the AUDIT cut-off levels. Twenty-six patients tested positive for UEtG and 29 for UEtS. HEtG identified ethanol intake of more than 20 g/d in 20 additional cases that did not appear in the AUDIT. Using the total score of the AUDIT, HEtG detected 14 additional cases of relevant alcohol intake. Conclusions: The findings of this study, which is the first assessing alcohol intake in HAT patients using direct ethanol metabolites and self reports, suggest the complementary use of both. Improved detection of hazardous or harmful alcohol consumption in the context of HCV and heroin dependence will allow for earlier intervention in this population. This ultimately will contribute to an improvement in quality of life of patients in HAT. Furthermore, a significant reduction of costs can be achieved through a reduction of complications caused by alcohol intake.

Yee LM; Wu D. False-positive amphetamine toxicology screen results in three pregnant women using labetalol. Obstetrics and Gynecology 117(2, Part 2 Supplement): 503-506, 2011. (8 refs.)

BACKGROUND: Labetalol is commonly used for control of hypertension in pregnancy. A component of the workup for new-onset hypertension in pregnancy often includes a urine drug screen. A labetalol metabolite is structurally similar to amphetamine and methamphetamine, thus causing potential cross-reactivity in drug immunoassays. CASES: We present one case of cocaine-induced hypertensive crisis superimposed on chronic hypertension and two cases of severe preeclampsia for which patients required escalating doses of labetalol for hypertension, with subsequent false-positive amphetamine urine drug screen results. CONCLUSION: In pregnant women requiring labetalol for treatment of hypertensive disease, a urine drug screen may be falsely positive for amphetamines and methamphetamines. Providers should be cognizant of this possibility when interpreting the results of urine drug screens.

Yonkers KA; Howell HB; Gotman N; Rounsaville BJ. Self-report of illicit substance use versus urine toxicology results from at-risk pregnant women. Journal of Substance Use 16(5): 372-380, 2011. (36 refs.)

Introduction: Many factors comprise a patient's decision to disclose use of drugs. Pregnant women may report drug use because they would like help with their addiction but the stigma associated with drug use may dampen their willingness to disclose. Knowledge about the accuracy of self-reported drug use as compared to urine toxicology screens can assist clinicians in the management of substance use in pregnancy. Method: We compared the urine toxicology screens and self-reported use of marijuana or cocaine for 168 women enrolled in an integrated obstetrical/substance abuse treatment program. We stratified by various periods of self-reported use and race and utilized Cohen's kappa to measure overall agreement between self-report and toxicology tests. Results: Most women with a positive toxicology screen reported use in the past 28 days (78% for marijuana, 86% for cocaine). However, many women reported their most recent use to be outside of the assays' detection window (14% for marijuana, 57% for cocaine). We did not find differences in self-report for women with positive urine between Whites and non-Whites (p = 1.00). Agreement over the previous month was good (Kappa = 0.74 and 0.70 for marijuana and cocaine, respectively.) Summary: A question about use of marijuana or cocaine during the preceding month rather than the prior few days may be a better indicator of use.