万氏牛黄清心缓释胶囊在比格犬体内药动学研究  

Study on Pharmacokinetics of Wanshi Niuhuang Qingxin Sustained-release Capsules in Beagle Dog

作　　者：田大丰[1] 李英 田晓琳[1] 王中彦[1] 

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016 [2]辽宁守正生物技术有限公司,辽宁沈阳110016

出　　处：《现代生物医学进展》2008年第6期1139-1141,共3页Progress in Modern Biomedicine

基　　金：沈阳市科技攻关项目(基金号:060466)

摘　　要：目的:研究比格犬单剂量交叉口服万氏牛黄清心缓释胶囊和市售普通丸给药的药动学。方法:采用高效液相色谱法测定10只比格犬单剂量口服万氏牛黄清心pH-依赖型梯度释药胶囊和市售丸后血浆中盐酸小檗碱的血药浓度。血浆样品采用碱化后乙醚萃取浓缩方法制备。以青藤碱为内标物质,流动相采用乙腈-0.1 mol·L^(-1)磷酸二氢钾溶液-磷酸(30:70:0.01),检测波长为262 nm,流速为1.0mL·min^(-1)。结果:血浆中内源性物质对盐酸小檗碱及青藤碱的测定无干扰;最低检出限为1.25 ng·mL^(-1);盐酸小檗碱在1.25～250ng·mL^(-1)浓度范围内线性关系良好,r=0.9990;绝对回收率为82.94%～88.36%,方法回收率为89.28%～92.29%;日内精密度RSD≤4.87%、日间精密度RSD≤7.03%。缓释胶囊和普通丸药动学参数AUC_(?)分别为668.02和809.95 h·ng·ml^(-1),MRT分别为5.27和4.34h,缓释胶囊相对于普通丸的生物利用度为84.6%。结论:建立的测定方法处理简单,无干扰,灵敏度高,适合测定中药缓释制剂的药物动力学研究。万氏牛黄清心缓释胶囊具有明显的缓释作用,药物在体内呈梯度释放。Objective To investigate the pharmacokinetics of Wanshi Niuhuang Qingxin sustained-release capsules and Wanshi Niuhuang Qingxin pills in Beagle dog. Methods Single dose of Wanshi Niuhuang Qingxin sustained-release capsules and Wanshi Niuhuang Qingxin pills were given to Beagle dog according to a randomized crossover design. Blood samples were prepared by alkalization, extraction with ether oxide and enrichment. The concentration of berberine hydrochloride in the plasma of beagle dog was determined by HPLC method, Kukoline was taken as internal standard, and the mobile phase was consisted of acetonitrile-potassium dihydrogen phosphate solution-phosphoric acid （30：70：0.01, v/v/v） with flow rate of 1.0 mL·min^-1. Results Berberine hydrochloride was separated completely without interference. The calibration curves were demonstrated to have good linear relation in the working range of 1.25 to 250 ng·mL^-1. The detection limit ofberberine hydrochloride in the plasma was 1.25 ng·mL^-1. The absolute recovery was 82.94% -88.36%, and the analytical recovery was 89.28%-92.29%. The within-day RSD and between-day RSD were less than 4.87% and 7.03% respectively. AUC0-∞ of tested capsules and reference pills were 668.02 and 809.95 h .ng.ml^-1, MRT 5.27 and 4.34 h, respectively. The relative bioavailability of tested capsules was 84,6 % compared with reference pills. Conclusion This method is simple and sensitive, and can be used in analyzing berberine hydrochloride in biological sample. The capsules have obviously sustained property.

关 键 词：万氏牛黄清心缓释胶囊 盐酸小檗碱 药动学 生物利用度 HPLC 

分 类 号：R969.1[医药卫生—药理学]