Canfell P C, Castagnoli N, Fahey M R, Hennis P J, Miller R D
Drug Metab Dispos. 1986 Nov-Dec;14(6):703-8.
This paper summarizes the results of studies of the metabolic fate of laudanosine, a major degradation product of atracurium. Intravenous bolus doses of laudanosine (1-3 mg/kg) were administered to eight dogs and two rabbits anesthetized with halothane, and urine and bile samples were collected for up to 6 hr. Urine samples also were collected from two surgical patients given repetitive doses of atracurium. Metabolites were isolated from all samples using C18-Sep Paks. Treatment of the isolates with beta-glucuronidase followed by purification of the hydrolysate by preparative liquid chromatography provided metabolite fractions which were characterized by analytical liquid chromatography and capillary gas chromatography combined with nitrogen-phosphorus and/or electron ionization-mass spectrometric detection. Reference compounds were employed as chromatographic retention time markers. O-Trimethylsilyl, O-tert-butyldimethylsilyl, and N-trifluoroacetyl derivatives of the metabolites and reference compounds were used for gas chromatographic and mass spectrometric analysis. In all three species, the following metabolites of laudanosine were identified: pseudocodamine (4'-desmethyllaudanosine), pseudolaudanine (6-desmethyllaudanosine), laudanine (3'-desmethyllaudanosine), codamine (7-desmethyllaudanosine), N-norlaudanosine, N-norpseudocodamine, and N-norpseudolaudanine.
本文总结了阿曲库铵的主要降解产物劳丹诺辛代谢命运的研究结果。给八只用氟烷麻醉的犬和两只兔静脉注射大剂量劳丹诺辛（1 - 3毫克/千克），并收集长达6小时的尿液和胆汁样本。还从两名接受重复剂量阿曲库铵的手术患者收集尿液样本。使用C18-Sep Paks从所有样本中分离代谢物。用β-葡萄糖醛酸酶处理分离物，然后通过制备液相色谱法纯化水解产物，得到代谢物馏分，通过分析液相色谱法和毛细管气相色谱法结合氮磷和/或电子电离质谱检测对其进行表征。使用参考化合物作为色谱保留时间标记。代谢物和参考化合物的O-三甲基硅烷基、O-叔丁基二甲基硅烷基和N-三氟乙酰基衍生物用于气相色谱和质谱分析。在所有三个物种中，鉴定出了以下劳丹诺辛的代谢物：假可待因（4'-去甲基劳丹诺辛）、假劳丹宁（6-去甲基劳丹诺辛）、劳丹宁（3'-去甲基劳丹诺辛）、可待因（7-去甲基劳丹诺辛）、N-去甲劳丹诺辛、N-去甲假可待因和N-去甲假劳丹宁。
