Borg Damon, Kolb Elizabeth, Lantigua Cindy, Stripp Richard
Cordant Health Solutions, 789 Park Ave., Huntington, NY 11743, USA.
J Anal Toxicol. 2018 Jan 1;42(1):25-32. doi: 10.1093/jat/bkx079.
Methamphetamine (MAMP) is a popular illicit drug abused for its central nervous system stimulating effects. MAMP is also used therapeutically in the treatment of overeating disorders, narcolepsy, attention deficit disorder, in over-the-counter (OTC) products to ease nasal congestion. MAMP exists in two enantiomeric forms, dextrorotary (d-MAMP) or levorotary (l-MAMP). The compounds are similar in chemical structure, simply differing in the orientation of functional groups around the asymmetric carbon. In part because of the availability of l-MAMP in OTC nasal inhalers, forensic guidelines require a sample to contain greater than 20% d-MAMP to consider illicit drug use when interpreting results. Standard analytical methods readily detect MAMP in biological specimens but cannot resolve the enantiomeric composition of the sample. Specialized analytical techniques based on chiral separation of the enantiomers are required to differentiate d-MAMP from l-MAMP. Our laboratory sought to develop and validate a method for the analysis of oral fluid specimens for d/l-MAMP using a chiral derivatizing agent and traditional reverse phase liquid chromatography tandem mass spectrometry (LC-MS-MS). MAMP was extracted from dilute oral fluid samples using Strata-XC solid phase extraction (SPE) cartridges and derivatized with Marfey's reagent. Chromatographic separation was achieved using Zorbax Eclipse Plus C18 columns. Linearity, accuracy and precision, recovery, matrix effects and specificity of the method were all within acceptable criteria. Intraday accuracy ranged from 93.3 to 103.4% and precision 0.1 to 1.6%. Interday accuracy ranged from 90.0 to 103.4% and precision 3.8 to 11.6%. Finally, having previously tested positive for MAMP using non-chiral analysis, 256 de-identified authentic oral fluid samples were analyzed using this validated method. 98% of all samples tested positive for d-MAMP at greater than 20%.
甲基苯丙胺（MAMP）是一种因具有中枢神经系统刺激作用而被滥用的流行非法药物。MAMP也被用于治疗暴饮暴食症、发作性睡病、注意力缺陷障碍，以及在非处方（OTC）产品中缓解鼻塞。MAMP以两种对映体形式存在，右旋（d-MAMP）或左旋（l-MAMP）。这些化合物化学结构相似，只是不对称碳周围官能团的方向不同。部分由于非处方鼻腔吸入器中存在l-MAMP，法医指南要求在解释结果时，样本中d-MAMP含量大于20%才考虑非法药物使用。标准分析方法能轻易检测生物样本中的MAMP，但无法解析样本的对映体组成。需要基于对映体手性分离的专门分析技术来区分d-MAMP和l-MAMP。我们实验室试图开发并验证一种使用手性衍生剂和传统反相液相色谱串联质谱（LC-MS-MS）分析口腔液样本中d/l-MAMP的方法。使用Strata-XC固相萃取（SPE）柱从稀释的口腔液样本中提取MAMP，并用Marfey试剂进行衍生化。使用Zorbax Eclipse Plus C18柱实现色谱分离。该方法的线性、准确度和精密度、回收率、基质效应和特异性均在可接受标准范围内。日内准确度范围为93.3%至103.4%，精密度为0.1%至1.6%。日间准确度范围为90.0%至103.4%，精密度为3.8%至11.6%。最后，对之前使用非手性分析检测MAMP呈阳性的256份身份不明的真实口腔液样本，使用这种经过验证的方法进行分析。所有样本中有98%检测出d-MAMP含量大于20%呈阳性。
