摘要
采用气相色谱/质谱联用法(GC-MS)鉴定安定在女性混合和Wistar大鼠肝微粒体中的代谢产物,推测安定在女性混合和大鼠肝微粒体中可能的代谢途径。在女性混合和Wistar大鼠肝微粒体中37℃恒温孵育48 h,固相萃取(SPE)净化提取,GC–MS(EI)检测。女性混合和Wistar大鼠肝微粒体中均可代谢生成6-氯-4-苯基喹唑啉、6-氯-2-甲基-4-苯基喹唑啉、2-甲氨基-5-氯-二苯甲酮、6-氯-4-苯基-2(1H)-喹唑啉酮、6-氯-1,4-二氢-1-甲基-4-苯基喹唑啉、去甲安定和6-氯-1,2-二氢-1-甲基-2-氧-4-苯基喹唑啉7种代谢物;此外,女性混合肝微粒体中检出替马西泮,而Wistar大鼠肝微粒体中检出5-羟基苯基安定。推测了安定在女性混合和Wistar大鼠肝微粒体(细胞色素P450酶系或者CYP450)中氧化、去甲基化等主要代谢途径和代谢特点,为进一步研究其代谢和代谢酶奠定基础。
A gas chromatography and mass spectrometric （GC - MS ） method was developed for the identification of diazepam and its metabolites in female pooled and Wistar rat liver microsomes, and probable metabolic pathways were speculated. The incubation system of diazepam was carried out at 37 ℃ for 48 h. The sample was hydrolyzed, and ex- tracted by solid phase extraction （SPE）. The metabolites were analyzed by GC-MS in EI mode. The experimental re- sults indicated that seven metabolites such as 6-chloro -4-phenylquinazoline, 6-chloro -2-methyl -4-phenylquinazo- line, 2-methylamino - 5-ehlorobenzophenone, 6-chloro - 4-phenyl - 2 （1H）-quinazolinone, 6-chloro - 1,4-dihydro - 1-methyl - 4-phenylquinazolin, nordazeparn and 6-chloro - 1,2-dihydro - 1-methyl - 2-oxo - 4-pheny- lquinazoline were detected in both female pooled and Wistar rat liver microsomes. Furthermore, temazepam was detec- ted in female pooled liver micresomes, and 5-Hydroxyphenyldiazepam was detected in Wistar rat liver microsomes. The study deduced main metabolic pathway and metabolic characteristic of diazepam in female pooled and Wistar rat liver microsomes （cytochrome P450 or CYP450 ）, including oxidation and demethylation, etc. In addition, it laid a solid foundation for further study of its metabolism and metabolic enzymes.
出处
《分析试验室》
CAS
CSCD
北大核心
2014年第1期64-68,共5页
Chinese Journal of Analysis Laboratory
基金
2013年广西公安科技研究与技术开发项目(GAT2013-2)资助
