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.docVIP

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 作者 作者单位 武静 山东大学齐鲁医院临床药理研究所， 山东 济南 250012 王本杰 山东大学齐鲁医院临床药理研究所， 山东 济南 250012 魏春敏 山东大学齐鲁医院临床药理研究所， 山东 济南 250012 孔祥麟 山东大学齐鲁医院临床药理研究所， 山东 济南 250012 郭瑞臣 山东大学齐鲁医院临床药理研究所， 山东 济南 250012 [ABSTRACT] Objective: To establish the HPLC method for determination of paeonol in human plasma and to evaluate the pharmacokinetic 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 160?mg paeonol was orally given to 20 healthy volunteers in a twoway crossover design test. The plasma samples were extracted with 300?μl acetonitrile. 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.