氯丙嗪在大鼠体内的代谢研究  

GC-MS Analysis of Chlorpromazine and Its Major Metabolites in Rat Urine

作　　者：张思敏[1] 黄克建[2] 李宏森[2] 刘晓锋[2] 李璐[2] 林翠梧[1] 

机构地区：[1]广西大学化学化工学院,广西南宁530004 [2]广西壮族自治区公安厅物证鉴定中心,广西南宁530012

出　　处：《分析测试学报》2011年第10期1088-1093,共6页Journal of Instrumental Analysis

基　　金：公安部应用创新计划项目(2007YYCXGXST081)

摘　　要：采用气相色谱-质谱法(GC-MS)检测大鼠尿液中的氯丙嗪及其代谢产物,并对其进行质谱解析,推测氯丙嗪在大鼠体内的代谢途径。通过对Wistar大鼠进行灌胃服用药物后收集24 h内尿样,经固相萃取(SPE)净化提取后,采用GC-MS(EI、PCI)检测。对比空白尿液与阳性尿液萃取液的质谱图,并根据质谱裂解规律鉴定其结构。实验结果表明:在大鼠尿液中共检出吩噻嗪、2-氯吩噻嗪、N-(2-丙烯基)-2-氯吩噻嗪、丙嗪、2-羟基吩噻嗪、去甲基氯丙嗪、2-氯-7-羟基吩噻嗪、2-氯吩噻嗪砜、3-羟基丙嗪、丙嗪亚砜、吩噻嗪砜、7-羟基氯丙嗪、氯丙嗪亚砜、去甲基氯丙嗪亚砜、N-乙酰基去甲基氯丙嗪、N-乙酰基-N-去二甲基氯丙嗪等多种代谢物,其中2-氯吩噻嗪、丙嗪、去甲基氯丙嗪、7-羟基氯丙嗪和氯丙嗪亚砜为主要代谢产物。推测了氯丙嗪在大鼠体内的氧化、还原等主要代谢途径。A gas chromatography and mass spectrometric （ GC - MS） method was developed for the determination of in vivo metabolism of chlorpromazine, and its mass chromatograms were analyzed. Five female Wistar rats were gavaged with ehlorpromazine hydrochloride and the 24-hr urine sample after administration were collected. The sample was hydrolyzed, and extracted by solid phase extrac- tion（SPE）. The metabolltes were analyzed by GC -MS under EI and PCI mode. The mass chromatograms of the parent drug, blank urine and the sample were compared and identified. Sixteen com- pounds such as phenothiazinc, 2-chlorophenothlazlne, N-（ 2-propcnyl ）-2-chlorophenothiazine, promazine, 2-hydroxylphenothiazine, demethylehlorpromazine, 3-hydroxylpromazine, promazine sulfoxide, 2-chloro-7-hydroxylphenothiazine, chlorophenothiazine sulfone, 7-hydroxylchlorpromazine, chlorpromazine sulfoxide, dihydroxylchlorpromazine, desmethylchlorpromazine sulfoxide, N- acetyl-demethylchlorpromazine, N-acetyl-dedimethylchlorpromazine were identified as metabolites, in which 2-chlorophenothiazine, promazine, demethylchlorpromazine, 7-hydroxylchlorpromazine and chlorpromazine sulfoxide were the main metabolites. The results suggested that at least three metabolic pathways for chlorpromazine, including oxidation, demethylation and dehalogenation, are operative in rats.

关 键 词：氯丙嗪 尿液 代谢物 气相色谱-质谱法(GC—MS) 质谱裂解 

分 类 号：O657.63[理学—分析化学] TQ460.72[理学—化学]