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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  );
  • 초록

    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.


  • 주제어

    Imidapril hydrochloride .   Quadruple mass spectrometry .   Bioavailability .   Human plasma .   SPE.  

  • 참고문헌 (10)

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    1. 1991 "Microencapsulation of Isoprinosine with Ethylcellulose" Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea 14 (4): 298~304    
    2. 1992 "수종의 붕해제가 살리실아미드정제의 제제특성에 미치는 영향" 藥劑學會誌 = Journal of Korean pharmaceutical sciences 22 (1): 41~48    
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    4. 1993 "Alginate Bead를 이용한 고분자 약물의 제어방출형 약물수송체" 藥劑學會誌 = Journal of Korean pharmaceutical sciences 23 (1): 19~26    
    5. 1993 "치아 연마용 인산일수소칼슘의 합성 및 물리화학적 성질" 약학회지 = Yakhak hoeji 37 (1): 66~75    
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    8. 1993 "오메프라졸 함유 직장좌제의 약물속도론적 연구" 약학회지 = Yakhak hoeji 37 (5): 427~436    
    9. 1994 "이온교환수지를 이용한 새로운 오메프라졸 복합체 개발" 약학회지 = Yakhak hoeji 38 (3): 250~264    
    10. 1995 "오메프라졸-에칠렌디아민 복합체를 이용한 제제설계" 藥劑學會誌 = Journal of Korean pharmaceutical sciences 25 (1): 19~29    

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