滋肾丸小檗碱和巴马汀在大鼠前列腺组织中的药动学研究  

Pharmacokinetic study for berberine and palmatine of Zishen Pills in rat prostate

作　　者：蔡飞[1,2] 孙亮[2] 彭玉初[1] 陈万生[2] 

机构地区：[1]广州军区机关门诊部,广东广州510080 [2]第二军医大学附属长征医院药学部,上海200003

出　　处：《广东药学院学报》2013年第5期488-493,共6页Academic Journal of Guangdong College of Pharmacy

基　　金：上海市科学技术委员会登山行动计划项目(07DZ19721)

摘　　要：目的建立LC-MS/MS法测定滋肾丸小檗碱和巴马汀在大鼠前列腺组织中的质量浓度,并进行药动学研究。方法液相色谱分离采用Zorbax SB-C18柱,以乙腈-质量分数0.3%甲酸溶液(体积比35∶65)为流动相,样品分析周期为3.5 min。质谱检测采用ESI离子源、MRM正离子模式。SD大鼠皮下注射丙酸睾酮复制前列腺增生模型,灌胃给予滋肾丸提取物1.94 g·kg-1,于不同时间点取前列腺组织,测定药物质量浓度并计算药动学参数。结果小檗碱和巴马汀在前列腺组织中1 h即达到较高的药物质量浓度,表现出双峰现象,2者的t max分别为8.00 h与8.67 h,t1/2分别为5.48 h与8.95 h,C max分别为24.6ng·g-1与27.8 ng·g-1,AUC0-t分别为302 ng·h·g-1与271 ng·h·g-1,MRT0-t分别为9.50 h与9.37 h,前列腺组织药物质量浓度显著高于相同给药剂量下血浆药物质量浓度。结论本方法可用于测定小檗碱和巴马汀在前列腺组织中的质量浓度,并应用于体内药动学研究。Objective A LC-MS/MS method was developed for the determination of berberine and palmatine of Zishen Pills （ZSP） in rat prostate, and applied for the pharmaeokinetie study. Methods The analytes were separated on a Zorbax SB-Cls column with the mobile phase of acetonitrile-0.3% formic acid （35： 65,Ф） in 3.5 min and detected by ESI mass spectrometry in positive MRM mode. SD rats were duplicated to benign prostate hyperplasia models by injecting with testosterone propionate and then administered orally with 1.94 g . kg^-1 of ZSP extract. The concentration of the analytes was determined after collection of the prostatic tissues and the pharmacokinetic parameters were calculated. Results The concentration of berberine and palmatine in prostatic tissues reached high levels in 1 h with double peaks. The tmax was 8.00 h and 8.67 h, tin was 5.48 h and 8.95 h,AUC0-t was 302 ng . h . g^-1 and 271 ng . h . g^-1 ,MRT0-t was 9.50 h and 9.37 h,respectively. The concentration of two alkaloids was more than that in plasma, Cmax, achieving 24.6 ng ~ g- 1 and 27.8 ng . g^-1, respectively. Conclusion The method was successfully applied to determine the concentration of the two alkaloids and assess the pharmacokinetics in rats.

关 键 词：滋肾丸 小檗碱 巴马汀 组织分布 药动学 LC—MS MS 

分 类 号：R285.5[医药卫生—中药学]