Liquid chromatographic-electrospray tandem mass spectrometric method for the simultaneous quantitation of the prodrug fosinopril and the active drug fosinoprilat in human serum

Citation
M. Jemal et De. Mulvana, Liquid chromatographic-electrospray tandem mass spectrometric method for the simultaneous quantitation of the prodrug fosinopril and the active drug fosinoprilat in human serum, J CHROMAT B, 739(2), 2000, pp. 255-271
Citations number
8
Categorie Soggetti
Chemistry & Analysis
Journal title
JOURNAL OF CHROMATOGRAPHY B
ISSN journal
13872273 → ACNP
Volume
739
Issue
2
Year of publication
2000
Pages
255 - 271
Database
ISI
SICI code
1387-2273(20000310)739:2<255:LCTMSM>2.0.ZU;2-N
Abstract
A sensitive, specific, accurate and reproducible LC-MS-MS method was develo ped and validated for the simultaneous quantitation of the prodrug fosinopr il and its active drug fosinoprilat in human serum. The method employed aci dification of the serum samples to minimize the hydrolysis of fosinopril to fosinoprilat prior to purification by solid-phase extraction to isolate th e two analytes and the two internal standards from human serum. The extract ed samples were analyzed by turbo ionspray LC-MS-MS in the positive ion mod e. Chromatography was performed on a polymer-based C-18 column (Asahipak(TM ) ODP PVA-C-18, 2x50 mm) using gradient elution with methanol and 10 mM amm onium acetate, pH 5.5. The calibration curve, 1.17 to 300 ng/ml, was fitted to a weighted (1/x) linear regression model. Serum quality control (QC) sa mples used to gauge the accuracy and precision of the method were prepared at concentrations of 5.00, 100, 250 and 500 ng/ml of each analyte, The inte r-assay accuracies were within 6% (DEV) for both analytes, The intra- and i nter-assay precisions were within 7% and 11% (RSD), respectively, for both analytes. The hydrolysis of fosinopril to fosinoprilat during sample proces sing was less than or equal to 6%. This degree of conversion would cause li ttle error in the analysis of post-dose serum samples since such samples ar e known to contain low levels of the prodrug compared to the drug. (C) 2000 Elsevier Science B.V. All rights reserved.