[The metabolic transformation of (-)-securinine].
OBJECTIVE
To study the in vitro and in vivo metabolism of (-)-securinine.


METHODS
The metabolic transformation of (-)-securinine was studied by using phenobarbital-induced rat liver microsomal incubate containing the NADPH-generating system in vitro and the constitution of the system was optimized. A reversed phase HPLC method was established to analyze the parent drug and its metabolites. The major metabolites were isolated and purified by liquid-liquid extraction, preparative TLC and HPLC, and their structures were elucidated as 6-hydroxyl securinine, 6-carbonyl securinine, 5 beta-hydroxyl securinine and 5 alpha-hydroxyl securinine by 1HNMR, 13CNMR and MS spectral analysis. An HPLC method was developed to analyze securinine and its metabolites in biofluids (bile, urine) of rat. The bile, urine and their enzymatic hydrolyzed samples of the rat i.p. administrated with (-)-securinine were determined by using this method.


RESULTS
Four main metabolites of (-)-securinine in rat hepatic microsome incubation were obtained and their structures were elucidated. Metabolites from in vitro study were confirmed in biofluids (bile, urine) which were collected from rats given securinine i.p. It was suggested that 6-hydroxyl securinine was excreted in conjugated form as well by analyzing enzymatic hydrolyzed bile.


CONCLUSIONS
The main metabolic pathway of (-)-securinine in vitro and in vivo is basically elucidated.
Li
Xiao-hai
XH
Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China.
Zhang
Jin-lin
JL
Zhou
Tong-hui
TH
D000470:Alkaloids / Q000302:isolation & purification / Q000378:metabolism* / Q000652:urine; D000818:Animals; D001381:Azepines / Q000302:isolation & purification / Q000378:metabolism* / Q000652:urine; D001646:Bile / Q000378:metabolism; D019665:Euphorbiaceae / Q000737:chemistry; D006576:Heterocyclic Compounds, 4 or More Rings / Q000302:isolation & purification / Q000378:metabolism* / Q000652:urine; D006572:Heterocyclic Compounds, Bridged-Ring; D066298:In Vitro Techniques; D007783:Lactones / Q000302:isolation & purification / Q000378:metabolism* / Q000652:urine; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D010880:Piperidines / Q000302:isolation & purification / Q000378:metabolism* / Q000652:urine; D010946:Plants, Medicinal / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism
D000470:Alkaloids; D001381:Azepines; D006576:Heterocyclic Compounds, 4 or More Rings; D006572:Heterocyclic Compounds, Bridged-Ring; D007783:Lactones; D010880:Piperidines; C000785:securinine