Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
Biomed Res Int. 2019 Aug 6;2019:7537618. doi: 10.1155/2019/7537618. eCollection 2019.
A high-throughput HPLC-MS/MS method was developed and validated for the determination of four antihypertensive drugs including metoprolol tartrate, hydrochlorothiazide, nifedipine, and valsartan in rat plasma. The Sprague-Dawley rats were randomly divided into three groups: A Group: gastric-administration of metoprolol tartrate, hydrochlorothiazide, nifedipine, or valsartan; B Group: a single intravenous injection of SXT, then dosing as the A group; C Group: daily injection of SXT through the tail vein for 8 consecutive days and dosing as the A group on the eighth day. For metoprolol tartrate and valsartan, blood samples were collected before administration and at time points 0.03, 0.08, 0.17, 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 h from the fossa orbitalis vein. For hydrochlorothiazide and nifedipine, the time points were 0, 0.08, 0.17, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, and 24 h. The plasma samples containing different individual antihypertensive drug were mixed and prepared by protein precipitation with methanol. The chromatographic separation was performed on an Agilent Eclipse Plus C18 column (2.1 mm×100 mm, 3.5 m) using gradient elution with mobile phase consisting of acetonitrile and water (containing 0.1% formic acid). The flow rate was 0.3 mL/min. The detection was accomplished on a tandem mass spectrometer with an electrospray ionization (ESI) source by multiple reaction monitoring (MRM) in both positive and negative modes. The method was successfully applied to a pharmacokinetic interaction study of Shuxuetong injection on the antihypertensive drugs. The results suggested that SXT could increase the total amount of metoprolol tartrate and nifedipine in plasma and showed little influence on the pharmacokinetic behaviors of hydrochlorothiazide and valsartan.
建立并验证了一种用于测定大鼠血浆中包括酒石酸美托洛尔、氢氯噻嗪、硝苯地平和缬沙坦在内的四种降压药的高效液相色谱-串联质谱法。Sprague-Dawley 大鼠被随机分为三组：A 组：灌胃给予酒石酸美托洛尔、氢氯噻嗪、硝苯地平和缬沙坦；B 组：单次尾静脉注射 SXT，然后按 A 组方案给药；C 组：连续 8 天每日经尾静脉注射 SXT，第 8 天按 A 组方案给药。对于酒石酸美托洛尔和缬沙坦，在眶下静脉采集给药前和 0.03、0.08、0.17、0.25、0.5、1、2、4、6、8、10、12 和 24 h 时的血样。对于氢氯噻嗪和硝苯地平，时间点为 0、0.08、0.17、0.25、0.5、0.75、1、2、4、6、8、10、12 和 24 h。含有不同个体降压药的混合血浆样品采用甲醇沉淀蛋白法制备。采用乙腈和水（含 0.1%甲酸）为流动相的 Agilent Eclipse Plus C18 柱（2.1mm×100mm，3.5μm）进行色谱分离。流速为 0.3mL/min。采用电喷雾电离（ESI）源，在正、负离子模式下，以多反应监测（MRM）进行串联质谱检测。该方法成功应用于疏血通注射液对降压药的药代动力学相互作用研究。结果表明，SXT 可增加酒石酸美托洛尔和硝苯地平在血浆中的总量，对氢氯噻嗪和缬沙坦的药代动力学行为影响较小。
