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LC-MS Determination and Bioavailability Study of Imidapril Hydrochloride after the Oral Administration of Imidapril Tablets in Human Volunteers  

Yun Ji Hye (NRL of Pharmaceutical Technology, College of Pharmacy, Chungnam National University)
Myung Ja Hye (NRL of Pharmaceutical Technology, College of Pharmacy, Chungnam National University)
Kim Hye Jin (NRL of Pharmaceutical Technology, College of Pharmacy, Chungnam National University)
Lee Sibeum (NRL of Pharmaceutical Technology, College of Pharmacy, Chungnam National University)
Park Jong-Sei (Lab Frontier, Co., Ltd.)
Kim Won (Lab Frontier, Co., Ltd.)
Lee Eun-Hee (Green Cross Reference Laboratory)
Moon Cheol Jin (Green Cross Reference Laboratory)
Hwang Sung-Joo (NRL of Pharmaceutical Technology, College of Pharmacy, Chungnam National University)
Publication Information
Archives of Pharmacal Research / v.28, no.4, 2005 , pp. 463-468 More about this Journal
Abstract
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, $Sep-pak^{R}$ C18, was used to extract imidapril and ramipril (an internal standard) from deproteinized plasma. The compounds were separated using a XTerra $MS^{R}$?C18 column ($3.5 {\mu}m, 2.1\times150 mm$) 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 $AUC_{12hr}$ of imidapril of $121.48\pm35.81 ng mL^{-1} h$, and $C_{max} and T_{max}$ values of $32.59\pm9.76 ng/mL and 1.75\pm0.27 h$. The developed method should be useful for the determination of imidapril in plasma with sufficient sensitivity and specificity in bioequivalence study.
Keywords
Imidapril hydrochloride; Quadruple mass spectrometry; Bioavailability; Human plasma; SPE;
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