title: Rapid and sensitive liquid chromatography/tandem mass spectrometry method for simultaneous determination of enalapril and its major metabolite enalaprilat, in human plasma: application to a bioequivalence study.
abstract: A rapid and most sensitive method for simultaneous determination of enalapril (ENP) and its metabolite, enalaprilat (ENPT), in human plasma using ESI-LC-MS/MS (electrospray ionization liquid chromatography tandem mass spectrometry) positive ion multiple reactions monitoring (MRM) mode, was developed and validated. The procedure involves a simple solid-phase extraction (SPE) followed by evaporation of the sample. Chromatographic separation was carried out on a Hypurity C(18) column (50 mm × 4.6 mm, 5 µm) with an isocratic mobile phase and a total run time of 2.0 min only. The MRM of ENP and ENPT is 377.10 → 234.20 and 349.20 → 206.10 respectively. The standard calibration curves showed excellent linearity within the range of 0.064 to 431.806 ng/mL for ENA and 0.064 to 431.720 ng/mL for ENPT (r ≥ 0.990). This is the only method which can quantitate upto 0.064 ng/mL for both ENP and ENPT in a single run with the shortest analysis time. In matrix effect experiment, this method shows a % CV (% coefficients of variation) of less than 5, which means that the proposed method is free from any kind of irregular ionization process. This method was successfully applied to a pharmacokinetic study after oral administration of enalapril maleate 20 mg tablet in Indian healthy male volunteers.
authors.affiliation: Bioanalytical Department, Cadila Pharmaceuticals Limited, 1389-Trasad road, Dholka, Gujarat, India. chinmoy_ghosh@yahoo.com
authors.forename: Chinmoy
authors.initials: C
authors.lastname: Ghosh
authors.forename: Ina
authors.initials: I
authors.lastname: Jain
authors.forename: Chandrakant P
authors.initials: CP
authors.lastname: Shinde
authors.forename: Bhaswat S
authors.initials: BS
authors.lastname: Chakraborty
mesh_terms: D000328:Adult; D000959:Antihypertensive Agents / Q000097:blood* / Q000302:isolation & purification; D002138:Calibration; D002853:Chromatography, Liquid / Q000191:economics / Q000379:methods; D004656:Enalapril / Q000097:blood* / Q000302:isolation & purification; D015773:Enalaprilat / Q000097:blood* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction / Q000191:economics / Q000379:methods; D021241:Spectrometry, Mass, Electrospray Ionization / Q000191:economics / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000191:economics / Q000379:methods*; D013997:Time Factors
chemical_list: D000959:Antihypertensive Agents; D004656:Enalapril; D015773:Enalaprilat