Mass spectrometric studies of cocaine disposition in animals and humans using stable isotope-labeled analogues.
Mass spectrometric studies of cocaine disposition in animals and humans using stable isotope-labeled analogues.
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使用稳定同位素标记的类似物对动物和人类中的可卡因处置进行质谱研究。
DOI：
10.1002/jps.2600781208
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发表时间：
1989
影响因子：
3.8
通讯作者：
Lutz,T
中科院分区：
文献类型：
--
作者：
Jindal,SP;Lutz,T
离子簇技术结合气相色谱-质谱（GC-MS）用于鉴定和定量大鼠和人体内主要代谢物可卡因（1a）。在一个典型的实验中，一只体重250 gm的雌性大鼠被腹腔注射20 mg/kg的混合物1a、ncd3可卡因（1b）、ocd3可卡因（1c）和42可卡因（1d）。收集尿液，用有机溶剂提取，用薄层色谱和高效液相色谱技术分离成几个部分。氚放射性在1中处于代谢稳定的位置，有助于分离代谢物，而氘标记1(b+c)，创建一个人工同位素簇，通过质谱解释提供特定的鉴定代谢物。去甲可卡因(2)、苯甲酰去甲甘碱(3)、n -羟去甲甘碱(4)、甲基去甲甘碱(5)、苯甲酰去甲甘碱（11）、去甲甘碱甲酯(9)、羟可卡因(7)、羟甲氧基可卡因（10）和二甲氧基羟可卡因(6)是大鼠尿液和血浆中的主要代谢物。全脑分析显示有大量未代谢的1和2，少量的9、5、7和10，以及微量的6。其中一些代谢物早前已被我们和其他研究者报道过，并在这项工作中得到了明确的证实。未代谢1a、其药理活性代谢物2和其他主要代谢物在大鼠脑、血浆和尿液中使用稳定同位素标记类似物作为内标和选择离子监测（SIM）质谱法进行定量分析。1和2的药代动力学特征表明其在脑和血浆中的半衰期<20分钟。这些数据与广泛报道的可卡因的短期行为效应很好地吻合。为动物研究开发的离子簇方法已成功地用于鉴定人类可卡因的代谢途径。用GC-MS和SIM分析了几个人的尿液样本，发现人的代谢谱与大鼠的相似。
Ion cluster technique in conjunction with gas chromatography-mass spectrometry (GC-MS) was used for the identification and quantitation major metabolites cocaine (1a) in rat and humans. In a typical experiment, a female rat weighing 250 gm was intraperitoneally administered a 20-mg/kg mixture1a, NCD3cocaine (1b), OCD3cocaine (1c), and 4T2cocaine (1d). The urine was collected, extracted with organic solvents, and separated into several fractions using TLC and HPLC techniques. Tritium radioactivity in a metabolically stable position in1dwas useful in the separation metabolites, while the deuterium labeled1(b+c), creating an artificial isotopic cluster, provided specific identification metabolites by mass spectrometric interpretation. Norcocaine (2), benzoylnorecgonine (3),N-hydroxynorcocaine (4), methylecgonidine (5), benzoylecgonine (11), ecgonine methyl ester (9), hydroxycocaine (7), hydroxymethoxycocaine (10), and dimethoxyhydroxycocaine (6) were found to be the major metabolites of1ain the rat urine as well as in plasma. The whole brain analysis showed significant amounts of unmetabolized1aand2, and minor concentrations of9,5,7, and10, and traces of6. Some of these metabolites have been reported earlier by us as well as other investigators and are unequivocally confirmed in this work. Unmetabolized1a, its pharmacologically active metabolite2, and other major metabolites were quantitated in the rat brain, plasma, and urine using stable isotope-labeled analogues as internal standards and selected ion monitoring (SIM) mass spectrometry. The pharmacokinetic profiles of1aand2indicate half-lives <20 min in the brain and plasma. These data are in good agreement with widely reported short-lived behavioral effects cocaine. The ion cluster methodology developed for the animal studies was successfully used in the identification metabolic pathways of cocaine in humans. Several human urine samples were analyzed using GC-MS and SIM procedures, and the metabolic profile in humans was found to be similar to the one in rat.