珍菊降压片在大鼠体内药动学研究

Pharmacokinetic Study of Zhenju Jiangya Pill in Rats

关键词:  珍菊降压片  芦丁  氢氯噻嗪  药动学  大鼠

Key words:  Zhenju Jiangya Pill  rutin  hydrochlorothiazide  pharmacokinetic  rats

摘要:

目的 建立同时测定大鼠血浆中芦丁和氢氯噻嗪的LC-MS/MS方法，并研究珍菊降压片在大鼠体内的药动学。方法 采用蛋白质沉淀法处理血浆样品，色谱柱为Pntulips BP-C₁₈柱（2.1 mm×50 mm，5μm），流动相为乙腈-水梯度洗脱，柱温为30℃；流速为0.45 mL·min^-1。采用电喷雾离子源，选择离子反应监测模式。采用DAS 2.0软件计算药动学参数。结果 方法学验证结果表明内源性杂质不干扰待测物和内标的测定，芦丁和氢氯噻嗪的线性范围分别为5~1 000 ng·mL^-1（r²=0.997 1）和2.5~500 ng·mL^-1（r²=0.995 8）。芦丁和氢氯噻嗪药动学参数：AUC_（0-t）为（107 157.31±38 056.63），（130 387.28±46 306.69）ng·mL^-1·min^-1；T_1/2z为（108.65±20.95），（240.86±46.44）min；T_max为（34.25±16.34），（120.00±0.00）min；C_max为（683.44±254.03），（368.45±136.95）ng·mL^-1。结论 该方法准确度、精密度、回收率和基质效应均符合生物基质样品测试要求，适用于珍菊降压片在大鼠体内的药动学研究。

Abstract:

OBJECTIVE To establish a LC-MS/MS method for the simultaneous determination of rutin and hydrochlorothiazide in rat plasma and to study the pharmacokinetics of Zhenju Jiangya Pill in rats. METHODS The plasma sample was handled by protein precipitation. The column was Pntulips BP-C₁₈ column(2.1 mm×50 mm, 5 μm) with the mobile phase of acetonitrile and water by gradient elution at 0.45 mL·min^-1. The column temperature was 30℃. The electrospray ion source and the ion reaction monitoring mode were used. DAS 2.0 software was used to calculate the pharmacokinetic parameters. RESULTS Methodological verification results showed that the endogenous impurities did not interfere with the determination of the analytes and internal standard. The linear ranges of rutin and hydrochlorothiazide were 5-1 000 ng·mL^-1(r²=0.997 1) and 2.5-500 ng·mL^-1(r²=0.995 8), respectively. The pharmacokinetic parameters of rutin and hydrochlorothiazide were as follows:AUC_(0-t) were (107 157.31±38 056.63), (130 387.28±46 306.69)ng·mL^-1·min, T_1/2z were (108.65±20.95), (240.86±46.44)min, T_max were (34.25±16.34), (120.00±0.00)min, C_max were (683.44±254.03), (368.45±136.95)ng·mL^-1. CONCLUSION The precision, accuracy, mean recoveries and the matrix effects were satisfied with the requirements of biological sample measurement. The method was successfully applied to the pharmacokinetic study of Zhenju Jiangya Pill in rats.