Determination of imidapril and imidaprilat in human plasma by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry.
A sensitive and specific assay of imidapril and its active metabolite, imidaprilat, in human plasma has been developed. This method is based on rapid isolation and high-performance liquid chromatography (HPLC)-electrospray ionization (ESI)-tandem mass spectrometry (MS-MS). Imidapril and imidaprilat were isolated from human plasma using OASIS HLB (solid-phase extraction cartridge), after deproteinization. The eluent from the cartridge was evaporated to dryness, and the residue was reconstituted in mobile phase and injected into the HPLC-ESI-MS-MS system. Each compound was separated on a semi-micro ODS column in acetonitrile-0.05% (v/v) formic acid (1:3, v/v). The selected ion monitoring using precursor-->product ion combinations of m/z 406-->234 and 378-->206, was used for determination of imidapril and imidaprilat, respectively. The linearity was confirmed in the concentration range of 0.2 to 50 ng/ml in human plasma, and the precision of this assay, expressed as a relative standard deviation, was less than 13.2% over the entire concentration range with adequate assay accuracy. The HPLC-ESI-MS-MS method correlates well with the radioimmunoassay method, therefore, it is useful for the determination of imidapril and imidaprilat with sufficient sensitivity and specificity in clinical studies.
Mabuchi
M
M
Tanabe R&D Service Co., Ltd., Osaka, Japan.
Kano
Y
Y
Fukuyama
T
T
Kondo
T
T
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D007093:Imidazoles / Q000097:blood*; D048289:Imidazolidines; D013058:Mass Spectrometry / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D000806:Angiotensin-Converting Enzyme Inhibitors; D007093:Imidazoles; D048289:Imidazolidines; C065166:imidapril; C078006:imidaprilat