清咽利膈丸大鼠体内给药后黄芩苷的药动学研究

Pharmacokinetics of Baicalin in Rats after Oral Administration of Qingyan Lige Pills by HPLC-MS-MS

摘要:

目的：采用高效液相色谱-串联质谱法（HPLC-MS-MS）研究清咽利膈丸给予大鼠后黄芩苷的药物代谢动力学。方法：以乙腈-0.2%甲酸水溶液 （24：76）为流动相，以木犀草素为内标，在ZOBAX SB-C₁₈ （2.1 mm×50 mm，3.5 μm）柱上进行分离，流速为 0.3 mL·min^-1。采用电喷雾离子源（ESI源）在正离子检测方式下进行多反应离子监测（MRM）。用于定量分析的离子反应分别为m/z 447.1→270.9（黄芩苷）和m/z 286.9→152.9 （木犀草素，内标）。结果：大鼠灌胃给予清咽利膈丸后，黄芩苷的达峰时间为2.4 h，峰质量浓度为0.59 mg·L^-1，浓度-时间曲线下面积为2.80 mg·L^-1·h^-1，半衰期为8.24 h。黄芩苷的药-时曲线呈现双峰。提示黄芩苷在体内存在肝-肠循环。结论：该方法专属性强，灵敏度高，药动学研究结果为清咽利膈丸的临床应用提供了参考。

Abstract:

Objective: To investigate the pharmacokinetics of baicalin in rats after oral administration of Qingyan Lige pills by HPLC-MS-MS. Method: With luteolin as the internal standard (IS), the analysis was carried out on a ZOBAX SB-C₁₈ (2.1 mm×50 mm, 3.5 μm) column using acetonitrile-0.2% formic acid (24 ：76) as the mobile phase. The detection was performed by means of electrospray ionization (ESI) mass spectrometry in positive ion mode with multiple reaction monitoring (MRM). Quantification was performed using the transitions of m/z 447.1→270.9 for baicalin, m/z 286.9→152.9 for IS. Result: After oral administration of Qingyan Lige pills to SD rats, the Tmax of baicalin was 2.4 h, the Cmax was 0.59 mg·L^-1, the AUC_0~∞ was 2.80 mg·L^-1·h and the t1/2 was 8.24 h. The plasma concentration-time curve exhibited double peak, which indicated that baicalin may have hepatoenteral circulation in vivo. Conclution: The method described in this report has high sensitivity and selectivity. The results of pharmacokinetic study on baicalin would be a suitable reference in clinical application for Qingyan Lige pills.