Koster Remco A, Alffenaar Jan-Willem C, Greijdanus Ben, VanDernagel Joanneke E L, Uges Donald R A
*Laboratory for Clinical and Forensic Toxicology and Drugs Analysis, Department of Hospital and Clinical Pharmacy, University of Groningen, University Medical Center Groningen; †SumID-Project, Zorgontwikkeling, Tactus Addiction Medicine, Deventer; and ‡ACSW-Nijmegen Institute for Scientist-Practitioners in Addiction, Radboud University, Nijmegen, The Netherlands.
Ther Drug Monit. 2014 Apr;36(2):234-43. doi: 10.1097/FTD.0b013e3182a377e8.
To facilitate the monitoring of drug abuse by patients, a method was developed and validated for the analysis of amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, methylenedioxyamphetamine, methylenedioxyethylamphetamine, methylphenidate, cocaine, benzoylecgonine, morphine, codeine, heroin, 6-monoacteylmorphine, methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), delta-9-tetrahydrocannabinol (THC), nicotine, and cotinine in human hair.
The hair preparation method contains a 3-step wash procedure with dichloromethane followed by a simultaneous hair pulverization and extraction procedure with disposable metal balls. The developed liquid chromatography tandem mass spectrometry method uses a single injection to detect and confirm all 17 abused drugs, including THC, within 4.8 minutes.
Nicotine was validated with a linear range of 800-25,000 pg/mg hair, and all other substances were validated with a linear range of 30.0-2500 pg/mg hair. For inaccuracy and imprecision, the overall bias did not exceed -8.2% and the overall coefficient of variation did not exceed 17.7%. Autosampler stability was proven for 48 hours at 10°C for all substances. Analytical cutoff concentrations were defined for each substance at the lowest validated inaccuracy and imprecision concentration with a bias and coefficient of variation within 15% and qualifier/quantifier ratios within 20% of the set ratio. The analytical cutoff concentrations were 200 pg/mg for codeine and 80.0 pg/mg for 6-MAM, heroin, EDDP, and THC. The analytical cutoff concentration for nicotine was 800 pg/mg and for all other validated substances 30.0 pg/mg. This method was successfully applied to analyze hair samples from patients who were monitored for drug abuse. Hair samples of 47 subjects (segmented into 129 samples) showed 3,4-methylenedioxymethamphetamine, methylphenidate, cocaine, benzoylecgonine, codeine, methadone, EDDP, THC, nicotine, and cotinine above the analytical cutoff.
The method was fully validated, including the validation of the qualifier/quantifier ratios. The analysis of real hair samples proved the efficacy of the developed method for monitoring drug abuse. The results obtained by this method provide the physician or health-care professional with extensive information about actual drug abuse or relapse and can be used for patient-specific therapy.
为便于监测患者的药物滥用情况，开发并验证了一种分析人发中苯丙胺、甲基苯丙胺、3,4-亚甲基二氧基甲基苯丙胺、亚甲基二氧基苯丙胺、亚甲基二氧基乙基苯丙胺、哌醋甲酯、可卡因、苯甲酰爱康宁、吗啡、可待因、海洛因、6-单乙酰吗啡、美沙酮、2-亚乙基-1,5-二甲基-3,3-二苯基吡咯烷（EDDP）、δ-9-四氢大麻酚（THC）、尼古丁和可替宁的方法。
毛发制备方法包括用二氯甲烷进行三步清洗程序，随后使用一次性金属球进行毛发粉碎和提取程序。所开发的液相色谱串联质谱法采用单次进样在4.8分钟内检测并确证所有17种滥用药物，包括THC。
尼古丁的线性范围为800 - 25,000 pg/mg毛发，其他所有物质的线性范围为30.0 - 2500 pg/mg毛发。对于不准确度和精密度，总体偏差不超过 -8.2%，总体变异系数不超过17.7%。所有物质在10°C下的自动进样器稳定性经证明可达48小时。为每种物质定义了分析截止浓度，该浓度为验证的最低不准确度和精密度浓度，偏差和变异系数在15%以内，定性/定量比在设定比值的20%以内。可待因的分析截止浓度为200 pg/mg，6 - MAM、海洛因、EDDP和THC的分析截止浓度为80.0 pg/mg。尼古丁的分析截止浓度为800 pg/mg，其他所有验证物质的分析截止浓度为30.0 pg/mg。该方法成功应用于分析接受药物滥用监测患者的毛发样本。47名受试者的毛发样本（分成129个样本）显示3,4-亚甲基二氧基甲基苯丙胺、哌醋甲酯、可卡因、苯甲酰爱康宁、可待因、美沙酮、EDDP、THC、尼古丁和可替宁高于分析截止浓度。
该方法已得到充分验证，包括定性/定量比的验证。实际毛发样本分析证明了所开发方法在监测药物滥用方面的有效性。通过该方法获得的结果为医生或医疗保健专业人员提供了有关实际药物滥用或复发的广泛信息，可用于针对患者的治疗。
