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)-氯吩噻嗪、丙嗪、2-羟基吩噻嗪、去甲基氯丙嗪、2-氯-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-乙酸基去甲基氯丙嗪、N-乙酸基-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 chlorpromazine hydrochloride and the 24-hr urine sample after administration were collected. The sample was hydrolyzed, and extracted by solid phase extraction ( SPE). The metabolites were analyzed by GC - MS under El and PCI mode. The mass chromatograms of the parent drug, blank urine and the sample were compared and identified. Sixteen compounds such as phenothiazine, 2-chlorophenothiazine, N-( 2-propenyl )-2-chlorophenothiazine, promazine, 2-hydroxylphenothiazine, demethylchlorpromazine, 3-hydroxylpromazine, promazine sulfoxide, 2-chloro-7-hydroxylphenothiazine, chlorophenothiazine sulfone, 7-hydroxylchlorproma-zine, 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.
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