title: LC-MS determination and bioavailability study of imidapril hydrochloride after the oral administration of imidapril tablets in human volunteers.
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 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 microm, 2.1 x 150 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.
authors.affiliation: NRL of Pharmaceutical Technology, College of Pharmacy, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejeon 305-764, Korea.
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Yun
authors.forename: Ja Hye
authors.initials: JH
authors.lastname: Myung
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Sibeum
authors.initials: S
authors.lastname: Lee
authors.forename: Jong-Sei
authors.initials: JS
authors.lastname: Park
authors.forename: Won
authors.initials: W
authors.lastname: Kim
authors.forename: Eun-Hee
authors.initials: EH
authors.lastname: Lee
authors.forename: Cheol Jin
authors.initials: CJ
authors.lastname: Moon
authors.forename: Sung-Joo
authors.initials: SJ
authors.lastname: Hwang
mesh_terms: D000284:Administration, Oral; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D006801:Humans; D048289:Imidazolidines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization; D013607:Tablets
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D048289:Imidazolidines; D013607:Tablets; C065166:imidapril