AB-FUBINACA M3 was reported to be a major metabolite of the drug, but its in vivo concentration in authentic human solid tissues has not been quantified yet. Another metabolite AB-FUBINACA M4 did not receive much attention previously and also has not been quantified yet in any authentic human specimens. The aims of this study are to establish a sensitive method for quantification of M3 and M4 in solid tissues and to compare the metabolite profile of AB-FUBINACA in authentic human specimens in vivo with that produced by human hepatocytes in vitro. The quantification was performed by liquid chromatography (LC)–quadrupole-ion trap-tandem mass spectrometry (MS-MS), and the characterization by LC–quadrupole Orbitrap MS-MS The limits of quantification of M3 were 10 pg/mL and 60 pg/g, and those of M4 were 100 pg/mL and 600 pg/g in urine and tissues, respectively. In the present work, M3 and M4 were identified and quantified in human lung, liver and kidney obtained from a cadaver for the first time; the concentrations of M3 were 226, 255, 202 and 155 pg/mL or g, and those of M4 14,400, 768, 637 and 1,390 pg/mL or g in urine, lung, liver and kidney, respectively. The peak intensity profiles of seven metabolites in these specimens were compared with that produced by human hepatocytes; the top three metabolites in urine specimen were completely different from those of hepatocytes. M3 was reported as the predominant metabolite in several previous works and M4 was listed as a minor metabolite in only one work, but, in this work, M4 has been found to be the major metabolite in all of the authentic urine, lung, liver and kidney specimens. The M3 plus M4 metabolites in lung or kidney were found most recommendable to prove AB-FUBINACA consumption, when urine specimen is lacking.

中文翻译：

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从滥用者处获得的固体组织中 AB-FUBINACA 主要代谢物的定量

据报道，AB-FUBINACA M3 是该药物的主要代谢物，但其在真实人体实体组织中的体内浓度尚未量化。另一种代谢物 AB-FUBINACA M4 以前没有受到太多关注，也没有在任何真实的人类标本中进行量化。本研究的目的是建立一种灵敏的定量实体组织中 M3 和 M4 的方法，并将真实人体标本中AB-FUBINACA 的代谢物谱与体外人肝细胞产生的代谢物谱进行比较. 通过液相色谱 (LC)-四极杆离子阱-串联质谱 (MS-MS) 进行定量，通过 LC-四极杆 Orbitrap MS-MS 进行表征 M3 的定量限为 10 pg/mL 和 60 pg /g，而 M4 在尿液和组织中分别为 100 pg/mL 和 600 pg/g。在目前的工作中，首次在从尸体中提取的人肺、肝脏和肾脏中鉴定并定量了 M3 和 M4；M3在尿液、肺、肝脏和肾脏中的浓度分别为226、255、202和155 pg/mL或g，M4分别为14,400、768、637和1,390 pg/mL或g。将这些样本中七种代谢物的峰值强度曲线与人类肝细胞产生的进行了比较；尿液标本中前三种代谢物与肝细胞完全不同。在之前的几项工作中，M3 被报告为主要代谢物，而 M4 仅在一项工作中被列为次要代谢物，但是，在这项工作中，M4 被发现是所有真实尿液、肺、肝脏和肝脏中的主要代谢物。肾脏标本。当缺乏尿液标本时，发现肺或肾脏中的 M3 加 M4 代谢物最适合证明 AB-FUBINACA 消耗。