Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Saarland University, 66421 Homburg (Saar), Germany.
Anal Bioanal Chem. 2010 Apr;396(7):2379-91. doi: 10.1007/s00216-009-3239-1. Epub 2009 Nov 10.
The Thai medicinal plant Mitragyna speciosa (Kratom in Thai) is misused as a herbal drug of abuse. During studies on the main Kratom alkaloid mitragynine (MG) in rats and humans, several dehydro analogs could be detected in urine of Kratom users, which were not found in rat urine after administration of pure MG. Questions arose as to whether these compounds are formed from MG only by humans or whether they are metabolites formed from the second abundant Kratom alkaloid paynantheine (PAY), the dehydro analog of MG. Therefore, the aim of the presented study was to identify the phase I and II metabolites of PAY in rat urine after administration of the pure alkaloid. This was first isolated from Kratom leaves. Liquid chromatography-linear ion trap mass spectrometry provided detailed structure information of the metabolites in the MS(n) mode particularly with high resolution. Besides PAY, the following phase I metabolites could be identified: 9-O-demethyl PAY, 16-carboxy PAY, 9-O-demethyl-16-carboxy PAY, 17-O-demethyl PAY, 17-O-demethyl-16,17-dihydro PAY, 9,17-O-bisdemethyl PAY, 9,17-O-bisdemethyl-16,17-dihydro PAY, 17-carboxy-16,17-dihydro PAY, and 9-O-demethyl-17-carboxy-16,17-dihydro PAY. These metabolites indicated that PAY was metabolized via the same pathways as MG. Several metabolites were excreted as glucuronides or sulfates. The metabolism studies in rats showed that PAY and its metabolites corresponded to the MG-related dehydro compounds detected in urine of the Kratom users. In conclusion, PAY and its metabolites may be further markers for a Kratom abuse in addition of MG and its metabolites.
泰国药用植物 Mitragyna speciosa（泰语中的 Kratom）被滥用于草药药物滥用。在对大鼠和人体中的主要 Kratom 生物碱 mitragynine（MG）的研究中，可以在 Kratom 使用者的尿液中检测到几种去氢类似物，但在给予纯 MG 后未在大鼠尿液中发现。人们开始怀疑这些化合物是否仅由人体从 MG 形成，或者它们是否是从第二种丰富的 Kratom 生物碱 paynantheine（MG 的去氢类似物）形成的代谢物。因此，本研究的目的是鉴定纯生物碱给药后大鼠尿液中的 PAY 及其代谢物。这是从 Kratom 叶子中首次分离出来的。液相色谱 - 线性离子阱质谱在 MS(n)模式下提供了有关代谢物的详细结构信息，尤其是高分辨率。除了 PAY 之外，还可以鉴定出以下 I 期代谢物：9-O-去甲基 PAY、16-羧基 PAY、9-O-去甲基-16-羧基 PAY、17-O-去甲基 PAY、17-O-去甲基-16,17-二氢 PAY、9,17-O-双去甲基 PAY、9,17-O-双去甲基-16,17-二氢 PAY、17-羧基-16,17-二氢 PAY 和 9-O-去甲基-17-羧基-16,17-二氢 PAY。这些代谢物表明 PAY 通过与 MG 相同的途径代谢。几种代谢物以葡萄糖醛酸或硫酸盐的形式排泄。大鼠代谢研究表明，PAY 及其代谢物与 Kratom 使用者尿液中检测到的 MG 相关去氢化合物相对应。总之，除了 MG 及其代谢物之外，PAY 及其代谢物可能是 Kratom 滥用的进一步标志物。
