Metabolism of the recently encountered designer drug, methylone, in humans and rats
Metabolism of the recently encountered designer drug, methylone, in humans and rats
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DOI：
10.1080/00498250600780191
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发表时间：
2006-08-01
期刊：
影响因子：
1.8
通讯作者：
Tsuchihashi, H.
中科院分区：
文献类型：
--
作者：
Kamata, H. T.;Shima, N.;Tsuchihashi, H.
采用气相色谱-质谱（GC-MS）和液相色谱-电喷雾电离质谱（LC-ESI MS）技术，对甲基酮滥用者和大鼠给药后的尿液样品进行分析，并采用标准品对甲基酮在人体和大鼠体内的代谢产物进行了研究。大鼠单次腹腔注射盐酸甲酮5 mg/kg后，进一步研究了甲酮及其三种代谢产物在大鼠体内的排泄规律。在人和大鼠中发现了两条主要的代谢途径：（1）通过N-去甲基化使侧链降解为相应的伯胺亚甲二氧基卡西酮（MDC），部分结合;和（2）苯环上的3-或4-OH基团的脱亚甲基化，然后O-甲基化，以产生4-羟基-3-甲氧基甲卡西酮（HMMC）或3-羟基-4-甲氧基甲卡西酮（3-OH-4-MeO-MC），大部分是共轭的。在这些代谢产物中，HMMC在人类和大鼠中含量最高。大鼠前48小时内尿中排泄的HMMC累积量约为剂量的26%，母体甲酮的量不超过3%。这些结果表明，HMMC的分析将是必不可少的证据，使用甲酮在法医尿液分析。
The urinary metabolites of methylone in humans and rats were investigated by analysing urine specimens from its abuser and after administrating to rats with gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-electrospray ionization mass spectrometry (LC-ESI MS), using authentic standards. The time-course excretion profiles of methylone and its three metabolites in rats were further investigated after a single intraperitoneal dosing of 5mg kg(-1) methylone hydrochloride. Two major metabolic pathways were revealed for both humans and rats as follows: (1) side-chain degradation by N-demethylation to the corresponding primary amine methylenedioxycathinone (MDC), partly conjugated; and (2) demethylenation followed by O-methylation of either a 3- or 4-OH group on the benzene ring to produce 4-hydroxy-3-methoxymethcathinone (HMMC) or 3-hydroxy-4-methoxymethcathinone (3-OH-4-MeO-MC), respectively, mostly conjugated. Of these metabolites, HMMC was the most abundant in humans and rats. The cumulative amount of urinary HMMC excreted within the first 48 h in rats was approximately 26% of the dose, and the amount of the parent methylone was not more than 3%. These results demonstrate that the analysis of HMMC will be indispensable for proof of the use of methylone in forensic urinalysis.