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Validated LC–MS/MS method for the simultaneous determination of enalapril maleate, nitrendipine, hydrochlorothiazide, and their major metabolites in human plasma
Author(s) -
Mohammad Mohammad AbdulAzim,
Mahrouse Marianne Alphonse,
Amer Enas Abdel Hakeem,
Elharati Nouran Saleh
Publication year - 2020
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.4955
Subject(s) - chemistry , chromatography , hydrochlorothiazide , protein precipitation , felodipine , active metabolite , metabolite , selected reaction monitoring , nitrendipine , therapeutic drug monitoring , liquid chromatography–mass spectrometry , electrospray ionization , pharmacokinetics , analyte , mass spectrometry , tandem mass spectrometry , pharmacology , blood pressure , endocrinology , biochemistry , medicine , organic chemistry , calcium
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 C 18 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 r 2 ≥ 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.