The purpose of the present study was to develop a standard protocol for imidapril hydrochloride bioequivalence testing. For this reason, a specific LC-MS method was developed and validated for the determination of imidapril in human plasma. A solid-phase extraction cartridge, Sep-pak® C18, was used to extract imidapril and ramipril (an internal standard) from deproteinized plasma. The compounds were separated using a XTerra MS® C18 column (3.5 μm, 2.1x150 mm) and acetonitrile-0.1% formic acid (67:33, v/v) adjusted to pH 2.4 by 2 mmol/L ammonium formic acid, as mobile phase at 0.3 mL/min. Imidapril was detected as m/z 406 at a retention time of ca. 2.3 min, and ramipril as m/z 417 at ca. 3.6 min. The described method showed acceptable specificity, linearity from 0.5 to 100 ng/mL, precision (expressed as a relative standard deviation of less than 15%), accuracy, and stability. The plasma concentration-versus-time curves of eight healthy male volunteers administered a single dose of imidapril (10 mg), gave an AUC12hr of imidapril of 121.48 ± 35.81 ng mL-1 h, and Cmax and Tmax values of 32.59 ± 9.76 ng/mL and 1.75 ± 0.27 h. The developed method should be useful for the determination of imidapril in plasma with sufficient sensitivity and specificity in bioequivalence study.
Bibliographical noteFunding Information:
The study was supported by KFDA (Korea Food and Drug Administration) and the Korean Ministry of Science and Technology through the National Research Laboratory Program (contract number:M1-0302-00-0016). The authors would like to thank the KFDA and Korean Ministry of Science and Technology for their continued support.
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Drug Discovery
- Organic Chemistry