In this study, solid tissues such as the lung, liver, kidney and urine were highlighted to profile the AB-PINACA in vivo metabolites in a fatal abuse case, although such metabolite analysis is usually made with urine specimens. We compared the relative peak intensities of in vivo metabolites of AB-PINACA in lung, liver, kidney and urine specimens collected at the autopsy of its abuser with its in vitro metabolites in human hepatocytes. The metabolites of AB-PINACA in tissues were extracted after homogenization. The urine specimen and portions of the extracted metabolites from tissues were firstly hydrolyzed with β-glucuronidase, and the metabolites were extracted. For in vitro experiment, AB-PINACA was incubated with human hepatocytes for 3 h to produce its metabolites. The identification of the in vivo and in vitro metabolites was performed using liquid chromatography (LC)–high-resolution Orbitrap-tandem mass spectrometry (MS-MS), and the relative intensities of these metabolites were measured using low resolution LC–quadrupole-ion trap-MS-MS. Thirteen metabolites of AB-PINACA were characterized in vivo in several human specimens and in in vitro human hepatocytes. They were produced by the terminal amide hydrolysis to carboxylic acid, hydroxylation, carbonyl formation and/or glucuronidation. The most detectable metabolite in the hepatocytes, lung or liver was the one produced by the terminal amide hydrolysis, whereas the top metabolite in the kidney or urine was the one produced by hydroxylation or carbonyl formation on the pentyl side chain after the terminal amide hydrolysis, respectively. At least 12 metabolites of AB-PINACA were detected in authentic human lung, liver or kidney specimen from a cadaver. It is concluded that the postmortem metabolite profiling of AB-PINACA can be fulfilled with solid tissues, and the lung and kidney were most recommendable especially when urine specimen is not available.

中文翻译：

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从其滥用者体内获得的AB-PINACA在体内的体内代谢产物：与体外实验的比较

在这项研究中，突出显示了在致命死亡病例中，诸如肺，肝，肾和尿等实体组织对AB-PINACA体内代谢产物进行了分析，尽管这种代谢产物分析通常是用尿液标本进行的。我们比较了滥用者尸体解剖收集的肺，肝，肾和尿标本中AB-PINACA体内代谢产物的相对峰值强度与人体肝细胞中的体外代谢产物。匀浆后提取组织中AB-PINACA的代谢产物。首先用β-葡糖醛酸糖苷酶水解尿液标本和从组织中提取的部分代谢物，然后提取代谢物。用于体外实验中，AB-PINACA与人肝细胞孵育3小时以产生其代谢产物。体内和体外代谢物的鉴定使用液相色谱（LC）-高分辨率Orbitrap串联质谱（MS-MS）进行，而这些代谢物的相对强度使用低分辨率LC-四极杆离子进行测量陷阱-MS-MS。AB-PINACA十三代谢物，其特征在于在体内在几种人类标本和在体外人肝细胞。它们是通过末端酰胺水解成羧酸，羟基化，羰基形成和/或葡糖醛酸化而产生的。肝细胞，肺或肝中最可检测到的代谢产物是末端酰胺水解产生的代谢产物，而肾脏或尿液中的最高代谢产物是末端酰胺水解后戊基侧链上的羟基化或羰基形成生成的代谢产物，分别。在尸体的真实人肺，肝或肾标本中检测到至少12种AB-PINACA代谢物。结论是，实体组织可以完成AB-PINACA的死后代谢产物谱分析，尤其是在没有尿液样本的情况下，肺和肾脏是最可取的。