Scheidweiler Karl B, Jarvis Michael J Y, Huestis Marilyn A
Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, 251 Bayview Boulevard Suite 200 Room 05A-721, Baltimore, MD, 21224, USA.
Anal Bioanal Chem. 2015 Jan;407(3):883-97. doi: 10.1007/s00216-014-8118-8. Epub 2014 Sep 16.
Clandestine laboratories constantly produce new synthetic cannabinoids to circumvent legislative scheduling efforts, challenging and complicating toxicological analysis. Sundstrom et al. (Anal Bioanal Chem 405(26):8463-8474, [9]) and Kronstrand et al. (Anal Bioanal Chem 406(15):3599-3609, [10]) published nontargeted liquid chromatography, high-resolution, quadrupole/time-of-flight mass spectrometric (LC-QTOF) assays with validated detection of 18 and 38 urinary synthetic cannabinoid metabolites, respectively. We developed and validated a LC-QTOF urine method for simultaneously identifying the most current 47 synthetic cannabinoid metabolites from 21 synthetic cannabinoid families (5-fluoro AB-PINACA, 5-fluoro-AKB48, 5-fluoro PB-22, AB-PINACA, ADB-PINACA, AKB48, AM2201, JWH-018, JWH-019, JWH-073, JWH-081, JWH-122, JWH-200, JWH-210, JWH-250, JWH-398, MAM2201, PB-22, RCS-4, UR-144, and XLR11). β-Glucuronidase-hydrolyzed urine was extracted with 1-mL Biotage SLE+ columns. Specimens were reconstituted in 150-μL mobile phase consisting of 80% A (0.1% formic acid in water) and 20% B (0.1% formic acid in acetonitrile). Fifty microliters was injected, and SWATH™ MS data were acquired in positive electrospray mode. The LC-QTOF instrument consisted of a Shimadzu UFLCxr system and an ABSciex 5600+ TripleTOF® mass spectrometer. Gradient chromatographic separation was achieved with a Restek Ultra Biphenyl column with a 0.5-mL/min flow rate and an overall run time of 15 min. Identification criteria included molecular ion mass error, isotopic profiles, retention time, and library fit criteria. Limits of detection were 0.25-5 μg/L (N = 10 unique fortified urine samples), except for two PB-22 metabolites with limits of 10 and 20 μg/L. Extraction efficiencies and matrix effects (N = 10) were 55-104 and -65-107%, respectively. We present a highly useful novel LC-QTOF method for simultaneously confirming 47 synthetic cannabinoid metabolites in human urine.
秘密实验室不断生产新的合成大麻素以规避立法监管，这给毒理学分析带来了挑战并使其变得复杂。桑德斯特伦等人（《分析与生物分析化学》405(26):8463 - 8474，[9]）以及克伦斯特兰德等人（《分析与生物分析化学》406(15):3599 - 3609，[10]）分别发表了非靶向液相色谱、高分辨率、四极杆/飞行时间质谱（LC - QTOF）分析方法，经验证可分别检测出18种和38种尿液中的合成大麻素代谢物。我们开发并验证了一种LC - QTOF尿液分析方法，用于同时鉴定来自21个合成大麻素家族的47种最新合成大麻素代谢物（5 - 氟AB - PINACA、5 - 氟 - AKB48、5 - 氟PB - 22、AB - PINACA、ADB - PINACA、AKB48、AM2201、JWH - 018、JWH - 019、JWH - 073、JWH - 081、JWH - 122、JWH - 200、JWH - 210、JWH - 250、JWH - 398、MAM2201、PB - 22、RCS - 4、UR - 144和XLR11）。用1 mL Biotage SLE + 柱提取经β - 葡萄糖醛酸酶水解的尿液。样品用由80% A（0.1%甲酸水溶液）和20% B（0.1%甲酸乙腈溶液）组成的150 μL流动相复溶。进样50 μL，在正电喷雾模式下采集SWATH™ MS数据。LC - QTOF仪器由岛津UFLCxr系统和ABSciex 5600 + TripleTOF®质谱仪组成。使用Restek超联苯柱以0.5 mL/min的流速进行梯度色谱分离，总运行时间为15分钟。鉴定标准包括分子离子质量误差、同位素分布、保留时间和库匹配标准。检测限为0.25 - 5 μg/L（N = 10个独特的加标尿液样品），除了两种PB - 22代谢物的检测限为10和20 μg/L。提取效率和基质效应（N = 10）分别为55 - 104%和 - 65 - 107%。我们提出了一种非常有用的新型LC - QTOF方法，用于同时确认人尿中的47种合成大麻素代谢物。
