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Walla Walla, DC, United States

Jeffery D.D.,Center for Healthcare Management Studies | Babeu L.A.,United Road Services | Nelson L.E.,Altarum Institute | Kloc M.,Drug Testing and Program Policy | Klette K.,Center for Healthcare Management Studies
Military Medicine

Objectives: This study identifies predictors of prescription drug misuse among U.S. active duty service members (ADSM). The 2008 Department of Defense Survey of Health-Related Behaviors (HRB) Among Active Duty Military Personnel indicated that ADSM misuse pain relievers, tranquilizers, sedatives, and stimulants at levels ranging from 2% to 17%. Methods: Secondary, multivariate analyses of HRB survey data examined predictors of self-reported prescription drug misuse for 4 distinct drug categories. Results: Receipt of a pain reliever prescription in the past month, year, or previous year were strong predictors (adjusted odds ratio above 2.0) of misuse for all drug categories; receipt of a prescription for anxiety or depression medication in the past year was the strongest predictor of sedative misuse (adjusted odds ratio = 4.46, 95% confidence intervals 3.18-6.24). Absence of a drug testing program was significantly related to the likelihood of drug misuse for all drug categories. Conclusions: ADSM with a history of treatment for pain and mood disorders, and who self-report headaches, sleep disorders, and fatigue are at higher risk for misusing prescription drugs, perhaps in an effort to self-manage symptoms. The results should be interpreted as a starting place for future exploration, not as the sole basis for policy or program development. © Association of Military Surgeons of the U.S. All rights reserved. Source

Battal D.,Mersin University | Barnes A.J.,U.S. National Institute on Drug Abuse | Castaneto M.S.,U.S. National Institute on Drug Abuse | Martin T.M.,Drug Testing and Program Policy | And 2 more authors.
Therapeutic Drug Monitoring

Mescaline, the primary psychoactive chemical in peyote cactus, has been consumed for thousands of years in ancient religious ceremonies. The US military wanted to determine if mescaline intake was a problem for personnel readiness. Twenty thousand seventeen urine specimens negative for cannabinoids, cocaine, opiates, and amphetamines were tested for mescaline with the Randox Drugs of Abuse V (DOA-V) biochip array immunoassay at the manufacturer's recommended cutoff of 6 mcg/L. A sensitive and specific method for mescaline quantification in urine was developed and fully validated. Extracted analytes were derivatized with pentafluoropropionic anhydride and pentafluoropropanol and quantified by gas chromatography-mass spectrometry (GC/MS) with electron impact ionization. Standard curves, using linear least squares regression with 1/x2 weighting, were linear from 1 to 250 mcg/L with coefficients of determination >0.994. Intra-and interassay imprecision was <4.4 coefficient of variation (%CV), with accuracies >90.4%. Mean extraction efficiencies were >92.0% across the linear range. This fully validated method was applied for the confirmation of urinary mescaline in 526 presumptivepositive specimens and 198 randomly selected presumptivenegative specimens at the manufacturer's 6 mcg/L cutoff. No specimen confirmed positive at the GC/MS limit of quantification of 1 mcg/L. Results indicated that during this time frame, there was insufficient mescaline drug use in the military to warrant routine screening in the drug testing program. However, mescaline stability, although assessed, could have contributed to lower prevalence. We also present a validated GC/MS method for mescaline quantification in urine for reliable confirmation of suspected mescaline intake. © 2015 Wolters Kluwer Health, Inc. All rights reserved. Source

Castaneto M.S.,U.S. National Institute on Drug Abuse | Castaneto M.S.,University of Maryland, Baltimore | Scheidweiler K.B.,U.S. National Institute on Drug Abuse | Gandhi A.,U.S. National Institute on Drug Abuse | And 5 more authors.
Drug Testing and Analysis

Synthetic cannabinoid intake is an ongoing health issue worldwide, with new compounds continually emerging, making drug testing complex. Parent synthetic cannabinoids are rarely detected in urine, the most common matrix employed in workplace drug testing. Optimal identification of synthetic cannabinoid markers in authentic urine specimens and correlation of metabolite concentrations and toxicities would improve synthetic cannabinoid result interpretation. We screened 20017 randomly collected US military urine specimens between July 2011 and June 2012 with a synthetic cannabinoid immunoassay yielding 1432 presumptive positive specimens. We analyzed all presumptive positive and 1069 negative specimens with our qualitative synthetic cannabinoid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, which confirmed 290 positive specimens. All 290 positive and 487 randomly selected negative specimens were quantified with the most comprehensive urine quantitative LC-MS/MS method published to date; 290 specimens confirmed positive for 22 metabolites from 11 parent synthetic cannabinoids. The five most predominant metabolites were JWH-018 pentanoic acid (93%), JWH-N-hydroxypentyl (84%), AM2201 N-hydroxypentyl (69%), JWH-073 butanoic acid (69%), and JWH-122N-hydroxypentyl (45%) with 11.1 (0.1-2,434), 5.1 (0.1-1,239), 2.0 (0.1-321), 1.1 (0.1-48.6), and 1.1 (0.1-250) μg/L median (range) concentrations, respectively. Alkyl hydroxy and carboxy metabolites provided suitable biomarkers for 11 parent synthetic cannabinoids; although hydroxyindoles were also observed. This is by far the largest data set of synthetic cannabinoid metabolites urine concentrations from randomly collected workplace drug testing specimens rather than acute intoxications or driving under the influence of drugs. These data improve the interpretation of synthetic cannabinoid urine test results and suggest suitable urine markers of synthetic cannabinoid intake. This article is a U.S. Government work and is in the public domain in the USA. Source

Spinelli E.,Federal University of Fluminense | Barnes A.J.,U.S. National Institute on Drug Abuse | Young S.,U.S. National Institute on Drug Abuse | Castaneto M.S.,U.S. National Institute on Drug Abuse | And 3 more authors.
Drug Testing and Analysis

Synthetic cannabinoids are marketed as legal alternatives to cannabis, as routine urine cannabinoid immunoassays do not detect synthetic cannabinoids. Laboratories are challenged to identify these new designer drugs that are widely available and represent a major public health and safety problem. Immunoassay testing offers rapid separation of presumptive positive and negative specimens, prior to more costly and time-consuming chromatographic confirmation. The Neogen SPICE ELISA kit targets JWH-018N-pentanoic acid as a marker for urinary synthetic cannabinoids. Assay performance was evaluated by analyzing 2469 authentic urine samples with the Neogen immunoassay and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Two immunoassay cut-off concentrations, 5 and 10μg/L, classified samples as presumptive positive or negative, followed by qualitative LC-MS/MS confirmation for 29 synthetic cannabinoids markers with limits of detection of 0.5-10μg/L to determine the assay's sensitivity, specificity and efficacy. Challenges at ±25% of each cut-off also were investigated to determine performance around the cut-off and intra- and inter-plate imprecision. The immunoassay was linear from 1 to 250μg/L (r2=0.992) with intra- and inter-plate imprecision of ≤5.3% and <9%, respectively. Sensitivity, specificity, and efficiency results with the 5μg/L cut-off were 79.9%, 99.7%, and 97.4% and with the 10μg/L cut-off 69.3%, 99.8%, and 96.3%, respectively. Cross-reactivity was shown for 18 of 73 synthetic cannabinoids markers evaluated. Good sensitivity, specificity, and efficiency, lack of sample preparation requirements, and rapid semi-automation documented that the Neogen SPICE ELISA kit is a viable method for screening synthetic cannabinoids in urine targeting JWH-018N-pentanoic acid. © 2014 John Wiley & Sons, Ltd. Source

Castaneto M.S.,U.S. National Institute on Drug Abuse | Castaneto M.S.,University of Maryland, Baltimore | Barnes A.J.,U.S. National Institute on Drug Abuse | Concheiro M.,U.S. National Institute on Drug Abuse | And 4 more authors.
Analytical and Bioanalytical Chemistry

Designer piperazines are emerging novel psychoactive substances (NPS) with few high-throughput screening methods for their identification. We evaluated a biochip array technology (BAT) immunoassay for phenylpiperazines (PNP) and benzylpiperazines (BZP) and analyzed 20,017 randomly collected urine workplace specimens. Immunoassay performance at recommended cutoffs was evaluated for PNPI (5 μg/L), PNPII (7.5 μg/L), and BZP (5 μg/L) antibodies. Eight hundred forty positive and 206 randomly selected presumptive negative specimens were confirmed by liquid chromatography high-resolution mass spectrometry (LC-HRMS). Assay limits of detection for PNPI, PNPII, and BZP were 2.9, 6.3, and 2.1 μg/L, respectively. Calibration curves were linear (R 2>0.99) with upper limits of 42 μg/L for PNPI/PNII and 100 μg/L for BZP. Quality control samples demonstrated imprecision <19.3 %CV and accuracies 86.0-94.5 % of target. There were no interferences from 106 non-piperazine substances. Seventy-eight of 840 presumptive positive specimens (9.3 %) were LC-HRMS positive, with 72 positive for 1-(3-chlorophenyl)piperazine (mCPP), a designer piperazine and antidepressant trazodone metabolite. Of 206 presumptive negative specimens, one confirmed positive for mCPP (3.3 μg/L) and one for BZP (3.6 μg/L). BAT specificity (21.1 to 91.4 %) and efficiency (27.0 to 91.6 %) increased, and sensitivity slightly decreased (97.5 to 93.8 %) with optimized cutoffs of 25 μg/L PNPI, 42 μg/L PNPI, and 100 μg/L BZP. A high-throughput screening method is needed to identify piperazine NPS. We evaluated performance of the Randox BAT immunoassay to identify urinary piperazines and documented improved performance when antibody cutoffs were raised. In addition, in randomized workplace urine specimens, all but two positive specimens contained mCPP and/or trazodone, most likely from legitimate medical prescriptions. © 2015 Springer-Verlag Berlin Heidelberg (outside the USA). Source

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