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

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 EI 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-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.