HPLC法测定丹皮酚血浓度及其胶囊与片剂人体生物等效性研究  

Pharmacokinetics and bioequivalence of paeonol capsules and tablets by the HPLC method

作　　者：武静[1] 王本杰[1] 魏春敏[1] 孔祥麟[1] 郭瑞臣[1] 

机构地区：[1]山东大学齐鲁医院临床药理研究所,山东济南250012

出　　处：《山东大学学报（医学版）》2007年第7期726-729,共4页Journal of Shandong University:Health Sciences

摘　　要：目的：建立HPLC法测定人血浆中丹皮酚的浓度,进行丹皮酚胶囊和片剂生物等效性研究。方法：采用双周期双交叉试验设计,20名健康男性志愿者随机单剂量口服丹皮酚胶囊或片剂160 mg,按设定时间采集肘静脉血,经乙睛萃取处理,以XB-C18（250 mm×4.6 mm,5μm）色谱柱为固定相,四氢呋喃-甲醇-水-磷酸（6∶60∶34∶0.1,V∶V）为流动相测定丹皮酚血浆浓度。采用DAS 2.0软件计算丹皮酚主要药代动力学参数,评价丹皮酚胶囊和片剂的生物等效性。结果：HPLC法测定血浆中丹皮酚的最低检测限为10 ng/ml,在10-500 ng/ml范围内线性关系良好（r=0.999 8）,日内、日间RSD均小于13.72%。丹皮酚胶囊和片剂主要药代动力学参数t1/2为（1.03±0.35）h和（1.09±0.62）h,Tmax为（1.02±0.13）h和（1.03±0.15）h,Cmax为（116.39±45.57）ng/ml和（111.16±41.24）ng/ml,AUC0~3为（173.91±45.41）ng.h/ml和（171.26±42.63）ng.h/ml,AUC0-∞为（217.13±56.55）ng.h/ml和（220.27±67.24）ng.h/ml。丹皮酚胶囊相对生物利用度F为（101.56±9.31）%。结论：建立的HPLC方法特异性强、灵敏度高,可用于丹皮酚血浓度测定和人体药动学研究。丹皮酚片剂、胶囊剂的主要药代动力学参数差异无统计学意义,符合生物等效性的假设,为生物等效制剂。Objective： To establish the HPLC method for determination of paeonol in human plasma and to evaluate the pharmacokinetie parameters and the bioequivalence of its capsules and tablets in healthy Chinese volunteers. Methods.. A liquor of plasma was collected at scheduled time points before and after a single dose of 160mg paeonol was orally given to 20 healthy volunteers in a two-way cross-over design test. The plasma samples were extracted with 300 μl aeetonitrile. The paeonol concentration in plasma was determined by HPLC method using a XB-C18 （250 mm × 4.6 mm, 5 μm） column as a stationary phase, and THF-methanol-water-phosphonic acid （6 ： 60 ： 34 ： 0.1, V ： V） as a mobile phase. The pharmacokinetic parameters were determined and the bioequivalence of paeonol capsules and tablets was evaluated with DAS 2.0. Results： The limit of detection for paeonol was 10 ng/ml, and a linearity obtained in the range of 10 - 500 ng/ml was excellent（ r = 0.999 8）. The relative standard deviations of intra-day and inter-day determination were less than 13.72%. The main pharmacokinetic parameters of paeonol after a single oral dose of 160 mg paeonol capsules and tablets were as follows： t1/2（h）1.03±0.35 and 1.09±0.62, Tmax（h）1.02±0.13 and 1.03±0.15, Cmax（ng/ml） 116.39 ± 45.57 and 111.16 ± 41.24, AUC0-3 （ng· h/ml） 173.91 ± 45.41 and 1.26 ± 42.63, AUC0-∞ （ng·h/ml） 217.13 ± 56.55 and 220.27 ± 67.24, respectively. The relative bioavailability of paeonol capsules was （ 101.56 ± 9.31） %. Conclusion： The established HPLC method is highly sensitive and accurate, and can be successfully used in the determination of plasma paeonol and is its pharmacokinetics studies. The pharmacokinetic parameter of paeonol shows no significant differences between capsules and tablets. The two preparations are bioequivalent.

关 键 词：丹皮酚 胶囊 片剂 色谱法 高压液相 

分 类 号：R917[医药卫生—药物分析学]