Department of Applied Chemistry, National Chiao Tung University, Hsinchu 30010, Taiwan.
Department of Forensic Toxicology, Institute of Forensic Medicine, Ministry of Justice, New Taipei City 235016, Taiwan.
J Anal Toxicol. 2022 Mar 21;46(3):246-256. doi: 10.1093/jat/bkab014.
Abuse of new psychoactive substances (NPS) has become a health and social issue of global concern. p-Methoxyamphetamine (PMA)/p-methoxymethamphetamine (PMMA) with fluoro- or chloro-derivatives of amphetamine and methamphetamine were among the most common drugs found in specimens from fatal cases in Taiwan during the January 2011 to December 2018 period. A liquid-liquid extraction sample preparation protocol with highly sensitive ultra-high performance liquid chromatography-tandem mass spectrometry approach was developed for the simultaneous analysis of seven phenethylamine-type drugs-PMA, PMMA, p-methoxyethylamphetamine, 4-fluoroamphetamine (4-FA), 4-fluoromethamphetamine (4-FMA), 4-chloroamphetamine (4-CA) and 4-chloromethamphetamine (4-CMA)-in postmortem blood and urine specimens. Separation by liquid chromatography was performed by Agilent Zorbax SB-Aq column. Tandem mass spectrometry was operated in Agilent Jet Stream Technology electrospray ionization in positive-ion multiple reaction monitoring mode. An analytical methodology was evaluated using drug-free blood and urine after fortification with 100-2,000 ng/mL of the seven target analytes. Average extraction recoveries were >80%; slightly higher ion suppression was observed for PMA and 4-CA; intra-/inter-day precision (% coefficient of variation) and accuracy were in the ranges of 0.52-12.3% and 85-110%, respectively. Limit of detection and lower limit of quantitation for these seven analytes were both in the 0.5-5 ng/mL range. Interference and carryover were not significant. This relatively simple methodology was found effective and reliable for routine identification and quantitation of these seven analytes in postmortem and antemortem blood and urine specimens received in 2018. Analytical data obtained from these actual cases indicated the following: (i) compared to findings reported during the 2007-2011 period, the use of substituted phenethylamine-type drugs decreased in 2018; (ii) ketamine and 7-aminonimetazepam (the main metabolite of nimetazepam) were the most common co-ingested substances in specimens containing PMA/PMMA, 4-FA/4-FMA, or 4-CA/4-CMA; and (iii) in drug fatalities, the concentration of PMA was significantly higher than the concentration of PMMA in both urine and blood, while the reverse was true in urine specimens from antemortem cases.
新型精神活性物质（NPS）滥用已成为全球关注的健康和社会问题。在 2011 年 1 月至 2018 年 12 月期间，台湾送检的尸检标本中发现了最常见的毒品，包括苯丙胺和甲基苯丙胺的氟代或氯代衍生物 p-甲氧基苯丙胺（PMA）/p-甲氧基苯丙胺（PMMA）。建立了一种灵敏的超高效液相色谱-串联质谱法，用于同时分析七种苯乙胺类药物-PMA、PMMA、p-甲氧基乙基苯丙胺、4-氟苯丙胺（4-FA）、4-氟甲氧基苯丙胺（4-FMA）、4-氯苯丙胺（4-CA）和 4-氯甲氧基苯丙胺（4-CMA）-在死后血液和尿液标本中。通过 Agilent Zorbax SB-Aq 柱进行液相色谱分离。串联质谱采用安捷伦喷射流技术在正离子多反应监测模式下进行电喷雾电离。通过在无药物的血液和尿液中加入 100-2000ng/ml 的七种目标分析物，对分析方法进行了评估。平均提取回收率＞80%；PMA 和 4-CA 的离子抑制稍高；日内/日间精密度（%变异系数）和准确度分别在 0.52-12.3%和 85-110%范围内。这七种分析物的检测限和定量下限均为 0.5-5ng/ml。无显著干扰和交叉污染。该相对简单的方法在 2018 年收到的死后和生前血液和尿液标本中，对这七种分析物的常规鉴定和定量是有效和可靠的。从这些实际案例中获得的分析数据表明：（i）与 2007-2011 年报告的数据相比，2018 年取代苯乙胺类药物的使用减少；（ii）在含有 PMA/PMMA、4-FA/4-FMA 或 4-CA/4-CMA 的标本中，最常见的共同摄入物质是氯胺酮和 7-氨基硝西泮（硝西泮的主要代谢物）；（iii）在药物致死病例中，尿液和血液中 PMA 的浓度均明显高于 PMMA，而生前病例的尿液标本则相反。
