Ramseier A, Caslavska J, Thormann W
Department of Clinical Pharmacology, University of Bern, Switzerland.
Electrophoresis. 1999 Sep;20(13):2726-38. doi: 10.1002/(SICI)1522-2683(19990901)20:13<2726::AID-ELPS2726>3.0.CO;2-6.
Data presented in this paper demonstrate that a competitive binding, electrokinetic capillary-based immunoassay previously used for screening of urinary amphetamine and analogs cannot be employed to distinguish between the enantiomers of amphetamine and methamphetamine. However, capillary zone electrophoresis with a pH 2.5 buffer containing (2-hydroxypropyl)-beta-cyclodextrin as chiral selector is shown to permit the enantioselective analysis of urinary extracts containing methamphetamine, amphetamine, 3,4-methylenedioxymethamphetamine (Ecstasy) and other designer drugs, and methadone together with its major metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine. In that approach, enantiomer identification is based upon comparison of extracted polychrome UV absorption data and electropherograms obtained by rerunning of spiked extracts with spectra and electropherograms monitored after extraction of fortified blank urine. The suitability of the described chiral electrokinetic capillary method for drug screening and confirmation is demonstrated via analysis of unhydrolyzed quality control urines containing a variety of drugs of abuse. Furthermore, in a urine of a patient under selegiline pharmacotherapy, the presence of the R-(-)-enantiomers of methamphetamine and amphetamine could be unambiguously identified. Direct intake of an R-enantiomer or ingestion of drugs that metabolize to the R-enantiomers can be distinguished from the intake of S-(+)-enantiomers (drug abuse) or prescribed drugs that metabolize to the S-enantiomers of methamphetamine and amphetamine. The described approach is simple, reproducible, inexpensive and reliable (free of interferences of other major basic drugs that are frequently found in toxicological urines) and could thus be used for screening for and confirmation of urinary enantiomers in a routine laboratory.
本文所呈现的数据表明,先前用于筛查尿中苯丙胺及其类似物的基于电动毛细管的竞争性结合免疫分析法,无法用于区分苯丙胺和甲基苯丙胺的对映体。然而,结果显示,以含有(2-羟丙基)-β-环糊精作为手性选择剂的pH 2.5缓冲液进行毛细管区带电泳,能够对含有甲基苯丙胺、苯丙胺、3,4-亚甲基二氧基甲基苯丙胺(摇头丸)及其他设计药物、美沙酮及其主要代谢物2-亚乙基-1,5-二甲基-3,3-二苯基吡咯烷的尿样提取物进行对映体选择性分析。在该方法中,对映体的鉴定是基于对提取的多色紫外吸收数据以及通过重新运行加标提取物获得的电泳图进行比较,其中加标提取物的光谱和电泳图是在强化空白尿样提取后进行监测的。通过对含有多种滥用药物的未水解质量控制尿样进行分析,证明了所描述的手性电动毛细管方法在药物筛查和确证方面的适用性。此外,在接受司来吉兰药物治疗的患者的尿液中,能够明确鉴定出甲基苯丙胺和苯丙胺的R-(-)-对映体。直接摄入R-对映体或摄入代谢为R-对映体的药物,可以与摄入S-(+)-对映体(药物滥用)或代谢为甲基苯丙胺和苯丙胺的S-对映体的处方药区分开来。所描述的方法简单、可重复、成本低廉且可靠(不受毒理学尿液中常见的其他主要碱性药物的干扰),因此可用于常规实验室中尿中对映体的筛查和确证。