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HPLC-MS를 이용한 생체시료 중 니세르골린의 주대사체인 10${alpha}$-Methoxy-9,10-dihydrolysergol(MDL)의 분석 및 이를 이용한 한국인 성인 남성에 대한 생체이용률 응용
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  • HPLC-MS를 이용한 생체시료 중 니세르골린의 주대사체인 10${alpha}$-Methoxy-9,10-dihydrolysergol(MDL)의 분석 및 이를 이용한 한국인 성인 남성에 대한 생체이용률 응용
  • Determination of 10${alpha}$-Methoxy-9,10-dihydrolysergol (MDL), Main Metabolite of Nicergoline, in Human Plasma by HPLC-MS and Applicability to Oral Bioavailability in Korean Healthy Male Volunteers
저자명
임현균,유선동,김경호,한상범,염정록,Lim. Hyon-Kyun,Yoo. Sun-Dong,Kim. Kyeong-Ho,Han. Sang-Beom,Youm. Jeong-Rok
간행물명
약학회지
권/호정보
2007년|51권 2호|pp.133-139 (7 pages)
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이 논문은 한국과학기술정보연구원과 논문 연계를 통해 무료로 제공되는 원문입니다.
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기타언어초록

A simple and sensitive HPLC-MS method for quantitation of 10${alpha}$-methoxy-9,10-dihydrolysergol (MDL), the main metabolite of nicergoline, in human plasma was developed and the bioavailability parameters of MDL was assessed in Korean healthy male volunteers. Clomipramine was used as an internal standard. MDL and internal standard in plasma sample were extracted using ethyl acetate. A centrifuged upper layer was then evaporated and reconstituted with mobile phase of 10 mM ammonium acetate-acetonitrile (10 : 90, v/v). The reconstituted samples were injected into a Zorbax SB-C8 column (2.1${ imes}$150 mm,5 ${mu}$m) at a flow-rate of 0.3 ml/min. Using MS with selected ion monitoring (SIM) mode, MDL and clomipramine were detected without severe interference from human plasma matrix. MDL produced a protonated molecular ion ([M+H]$^+$) at m/z 287. Internal standard produced a protonated molecular ion ([M+H]$^+$) at m/z 315. A linear relationship for MDL was found in the range of 2.5${sim}$100 ng/ml. The lower limit of quantitation (LLOQ) was 2.5 ng/ml with acceptable precision and accuracy. The intra- and inter-day validation for all coefficients of variation (R.S.D.%) were found less than 15%. Main pharmacokinetic parameters of 30 mg of nicergoline were revealed as follows: AUC$_t$ 321.1${pm}$64.5 ng${cdot}$hr/ml, C$_{max}$, 51.2${pm}$25.3 ng/ml, T$_{max}$ 3.6${pm}$1.5 hr, K$_{el}$ 0.12${pm}$0.07 hr$^{-1}$ and t$_{1/2}$ 7.6${pm}$3.4 hr. Inter subject variations and race differences were shown in comparison with the published data in the literature.