Studies on the metabolism and toxicological detection of glaucine, an isoquinoline alkaloid from Glaucium flavum (Papaveraceae), in rat urine using GC-MS, LC-MSn and LC-high-resolution MSn
Studies on the metabolism and toxicological detection of glaucine, an isoquinoline alkaloid from Glaucium flavum (Papaveraceae), in rat urine using GC-MS, LC-MSn and LC-high-resolution MSn
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DOI：
10.1002/jms.3112
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发表时间：
2013-01-01
影响因子：
2.3
通讯作者：
Maurer, Hans H.
中科院分区：
文献类型：
--
作者：
Meyer, Golo M. J.;Meyer, Markus R.;Maurer, Hans H.
甘氨酸((S)-5，6，6a，7-tetrahydro-1，2，9，10-tetramethoxy-6-methyl-4H-dibenzo[de，g]喹啉(Glaucine[de，g]Quinoline)是一种异喹啉生物碱，为罂粟科植物黄花的主要成分。它被描述为单独或与其他药物结合使用的消遣药物。此外，在保加利亚和其他国家，蓝豆碱被用作治疗药物和止咳药。目前，还没有关于蓝花碱的代谢和毒理学分析的数据。为了研究两者的关系，给Wistar大鼠灌胃灌胃蓝花碱，并采集尿液。对于新陈代谢研究，尿样的工作包括蛋白质沉淀或酶裂解，然后固相萃取。样品随后通过与低或高分辨率质谱仪(HR-MS)联用的液相色谱(LC)进行测定。通过对相应碎片的详细解释鉴定了I相和II相代谢物，并通过HR-MS测定其元素组成进一步证实了这些碎片。根据这些数据，可以提出以下代谢途径：2、9和10位的O-脱甲基化，N-脱甲基化、羟化、N-氧化及其组合，以及酚类代谢物的葡萄糖醛酸化和/或硫酸盐化。为了在滥用或中毒的情况下监测蓝绿色物质的摄入量，O-和N-脱甲基代谢物是作者所述的气相色谱-MS和LC-MSN筛选方法的主要目标。这两种方法都允许在相当于普通滥用者剂量的2毫克/公斤体重剂量后，确认老鼠尿液中摄取了蓝藻氨酸。版权所有(C)2013 John Wiley&Sons，Ltd.
Glaucine ((S)-5,6,6a,7-tetrahydro-1,2,9,10-tetramethoxy-6-methyl-4H-dibenzo [de,g]quinoline) is an isoquinoline alkaloid and main component of Glaucium flavum (Papaveraceae). It was described to be consumed as recreational drug alone or in combination with other drugs. Besides this, glaucine is used as therapeutic drug in Bulgaria and other countries as cough suppressant. Currently, there are no data available concerning metabolism and toxicological analysis of glaucine. To study both, glaucine was orally administered to Wistar rats and urine was collected. For metabolism studies, work-up of urine samples consisted of protein precipitation or enzymatic cleavage followed by solid-phase extraction. Samples were afterwards measured by liquid chromatography (LC) coupled to low or high-resolution mass spectrometry (HR-MS). The phase I and II metabolites were identified by detailed interpretation of the corresponding fragmentations, which were further confirmed by determination of their elemental composition using HR-MS. From these data, the following metabolic pathways could be proposed: O-demethylation at position 2, 9 and 10, N-demethylation, hydroxylation, N-oxidation and combinations of them as well as glucuronidation and/or sulfation of the phenolic metabolites. For monitoring a glaucine intake in case of abuse or poisoning, the O- and N-demethylated metabolites were the main targets for the gas chromatography-MS and LC-MSn screening approaches described by the authors. Both allowed confirming an intake of glaucine in rat urine after a dose of 2 mg/kg body mass corresponding to a common abuser's dose. Copyright (c) 2013 John Wiley & Sons, Ltd.