title: Greener bioanalytical approach for LC/MS-MS assay of enalapril and enalaprilat in human plasma with total replacement of acetonitrile throughout all analytical stages.
abstract: Green bioanalytical approaches are oriented toward minimization or elimination of hazardous chemicals associated to bioanalytical applications. LC/MS-MS assay of enalapril and enalaprilat in human plasma was achieved by elimination of acetonitrile from both sample preparation and chromatographic separation stages. Protein precipitation (PP) by acetonitrile addition was replaced by liquid-liquid extraction (LLE) in 1-octanol followed by direct large volume injection of the organic layer in the chromatographic column operated under reversed phase (RP) separation mechanism. At the mean time, acetonitrile used as organic modifier in the mobile phase was successfully replaced by a mixture of propylene carbonate/ethanol (7/3, v/v). Three analytical alternatives ((I) acetonitrile PP+acetonitrile based chromatographic elution; (II) 1-octanol LLE+acetonitrile based chromatographic elution; (III) 1-octanol LLE+propylene carbonate/ethanol based chromatographic elution) were validated and the quality characteristics were compared. Comparison between these alternative analytical approaches was also based on results obtained on incurred samples taken during a bioequivalence study, through application of the Bland-Altman procedure.
authors.affiliation: University of Bucharest, Faculty of Chemistry, Department of Analytical Chemistry, Bucharest 050663, Romania.
authors.forename: Mihaela
authors.initials: M
authors.lastname: Cheregi
authors.forename: Florin
authors.initials: F
authors.lastname: Albu
authors.forename: Ştefan
authors.initials: Ş
authors.lastname: Udrescu
authors.forename: Nicoleta
authors.initials: N
authors.lastname: Răducanu
authors.forename: Andrei
authors.initials: A
authors.lastname: Medvedovici
mesh_terms: D020003:1-Octanol / Q000737:chemistry; D000097:Acetonitriles / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods*; D018592:Cross-Over Studies; D004656:Enalapril / Q000097:blood* / Q000737:chemistry / Q000302:isolation & purification; D015773:Enalaprilat / Q000097:blood* / Q000737:chemistry / Q000302:isolation & purification; D000431:Ethanol / Q000737:chemistry; D055772:Green Chemistry Technology / Q000379:methods*; D006801:Humans; D016014:Linear Models; D059625:Liquid-Liquid Extraction; D011407:Propane / Q000031:analogs & derivatives / Q000737:chemistry; D016032:Randomized Controlled Trials as Topic; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013810:Therapeutic Equivalency; D014867:Water / Q000737:chemistry
chemical_list: D000097:Acetonitriles; D014867:Water; D000431:Ethanol; D004656:Enalapril; C045990:propylene carbonate; D015773:Enalaprilat; D020003:1-Octanol; D011407:Propane; C032159:acetonitrile