Hypertension is a major risk factor for atherosclerosis and ischemic heart disease. Most hypertensive patients need a combination of antihypertensive agents to achieve therapeutic goals. A rapid, sensitive, and selective liquid chromatography‐tandem mass spectrometric method was developed and validated for simultaneous determination of enalapril maleate (ENA) and its major metabolite enalaprilat (ENAT), nitrendipine (NIT) and its major metabolite dehydronitrendipine (DNIT), and hydrochlorothiazide (HCT) in human plasma using felodipine as an internal standard (IS). The drugs were extracted from plasma using one‐step protein precipitation. Chromatographic separation was performed on a Symmetry C₁₈ column, with water and acetonitrile (10:90, v/v) as mobile phase. The detection was carried out using multiple reaction monitoring mode and coupled with electrospray ionization source. Multiple reaction monitoring transitions were m/z 377.1 → 234.1 for ENA, m/z 349.2 → 206.1 for ENAT, m/z 361.2 → 315.1 for NIT, m/z 359 → 331 for DNIT, m/z 295.9 → 205.1 for HCT, and m/z 384.1 → 338 for felodipine (IS). The method was linear over concentration ranges of 1–200, 20–500, 5–200, 2–100, and 5–200 ng/mL for ENA, ENAT, NIT, DNIT, and HCT, respectively, with r² ≥ 0.99. Method validation was performed according to U.S. Food and Drug Administration guidelines. The validated method showed good sensitivity and selectivity and could be applied for therapeutic drug monitoring and bioequivalence studies.

中文翻译：

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经验证的LC-MS / MS方法可同时测定人血浆中的马来酸依那普利，尼群地平，氢氯噻嗪及其主要代谢物。

高血压是动脉粥样硬化和缺血性心脏病的主要危险因素。大多数高血压患者需要联合使用降压药才能达到治疗目的。建立了快速，灵敏和选择性的液相色谱-串联质谱方法，并验证了该方法可同时测定马来酸依那普利（ENA）及其主要代谢物依那普利拉（ENAT），尼群地平（NIT）及其主要代谢物脱氢尼地平（DNIT）和使用非洛地平作为内标（IS）的人类血浆中的氢氯噻嗪（HCT）。使用一步蛋白沉淀从血浆中提取药物。色谱分离是在Symmetry C _{18上进行的}柱，用水和乙腈（10：90，v / v）作为流动相。使用多反应监测模式并与电喷雾电离源耦合进行检测。多重反应监测转换为ENA为m / z 377.1→234.1，ENAT为m / z 349.2→206.1 ，NIT为m / z 361.2→315.1 ，DNIT为m / z 359→331 ，HCT为m / z 295.9→205.1，和M / Z 384.1→338非洛地平（IS）。对于ENA，ENAT，NIT，DNIT和HCT，该方法在浓度范围分别为1–200、20–500、5–200、2–100和5–200 ng / mL时是线性的，r ²≥0.99。方法验证是根据美国食品药品监督管理局的指导进行的。经验证的方法显示出良好的敏感性和选择性，可用于治疗药物监测和生物等效性研究。