Hutter Melanie, Broecker Sebastian, Kneisel Stefan, Franz Florian, Brandt Simon D, Auwarter Volker
Institute of Forensic Medicine, Forensic Toxicology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Albertstr. 9, 79104 Freiburg, Germany.
Broeckers Solutions, Dyrotzer Straße 8, 13583 Berlin, Germany.
Curr Pharm Biotechnol. 2018;19(2):144-162. doi: 10.2174/1389201019666180509163114.
Herbal mixtures containing synthetic cannabinoid receptor agonists (SCRAs) are promoted as legal alternative to marihuana and are easily available via the Internet. Keeping analytical methods for the detection of these SCRAs up-to-date is a continuous challenge for clinicians and toxicologists due to the high diversity of the chemical structures and the frequent emergence of new compounds. Since many SCRAs are extensively metabolized, analytical methods used for urine testing require previous identification of the major metabolites of each compound.
The aim of this study was to identify the in vivo major metabolites of nine SCRAs (AM- 694, AM-2201, JWH-007, JWH-019, JWH-203, JWH-307, MAM-2201, UR-144, XLR-11) for unambiguous detection of a drug uptake by analysis of urine samples.
Positive urine samples from patients of hospitals, detoxification and therapy centers as well as forensic-psychiatric clinics were analyzed by means of liquid chromatography-tandem mass spectrometry (LC-MS/MS) and liquid chromatography-quadrupole time-of-flight mass spectrometry (LCqToF- MS) for investigation of the major in vivo metabolites.
For all investigated SCRAs, monohydroxylation, dihydroxylation and/or formation of the Nhexanoic/ pentanoic acid metabolites were among the most abundant metabolites detected in human urine samples. Substitution of the fluorine atom was observed to be an important metabolic reaction for compounds carrying an N-(5-fluoropentyl) side chain. N-Dealkylated metabolites were not detected in vivo.
The investigated metabolites facilitate the reliable detection of drug uptake by analysis of urine samples. For distinction between uptake of the fluorinated and the non-fluorinated analogs, the N-(4-hydroxypentyl) metabolite of the non-fluorinated analog was identified as a useful analytical target and consumption marker.
含有合成大麻素受体激动剂（SCRAs）的草药混合物被宣传为大麻的合法替代品，并且可以通过互联网轻松获取。由于化学结构的高度多样性以及新化合物的频繁出现，保持用于检测这些SCRAs的分析方法的更新对临床医生和毒理学家来说是一项持续的挑战。由于许多SCRAs会被广泛代谢，用于尿液检测的分析方法需要预先鉴定每种化合物的主要代谢物。
本研究的目的是鉴定九种SCRAs（AM-694、AM-2201、JWH-007、JWH-019、JWH-203、JWH-307、MAM-2201、UR-144、XLR-11）的体内主要代谢物，以便通过分析尿液样本明确检测药物摄入情况。
通过液相色谱-串联质谱（LC-MS/MS）和液相色谱-四极杆飞行时间质谱（LCqToF-MS）分析来自医院、戒毒和治疗中心以及法医精神病诊所患者的阳性尿液样本，以研究主要的体内代谢物。
对于所有研究的SCRAs，单羟基化、二羟基化和/或N-己酸/戊酸代谢物的形成是在人类尿液样本中检测到的最丰富的代谢物之一。观察到氟原子的取代是携带N-（5-氟戊基）侧链的化合物的重要代谢反应。体内未检测到N-去烷基化代谢物。
所研究的代谢物有助于通过分析尿液样本可靠地检测药物摄入情况。为了区分氟化和非氟化类似物的摄入情况，非氟化类似物的N-（4-羟基戊基）代谢物被鉴定为有用的分析靶点和消费标志物。
Zotero 插件