Validated LC-MS/MS method for the simultaneous determination of enalapril maleate, nitrendipine, hydrochlorothiazide, and their major metabolites in human plasma.
Mohammad Abdul-Azim MohammadMarianne Alphonse MahrouseEnas Abdel Hakeem AmerNouran Saleh ElharatiPublished in: Biomedical chromatography : BMC (2020)
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.
Keyphrases
- simultaneous determination
- liquid chromatography
- tandem mass spectrometry
- liquid chromatography tandem mass spectrometry
- mass spectrometry
- high performance liquid chromatography
- blood pressure
- high resolution mass spectrometry
- solid phase extraction
- hypertensive patients
- ultra high performance liquid chromatography
- cardiovascular disease
- drug administration
- cell cycle arrest
- loop mediated isothermal amplification
- gas chromatography
- cell death
- ms ms
- risk assessment
- high resolution
- public health
- signaling pathway
- amino acid
- quantum dots
- clinical practice