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KMID : 0370220070510020133
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Yakhak Hoeji
2007 Volume.51 No. 2 p.133 ~ p.139
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Determination of 10α-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
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Lim Hyon-Kyun
Youm Jeong-Rok
Kim Kyeong-Ho
Yoo Sun-Dong
Han Sang-Beom
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Abstract
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A simple and sensitive HPLC-MS method for quantitation of 10α-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 (2.1×150 mm,5 μm) 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 2.5~100 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: AUCt 321.1±64.5 ng ·hr/ml, Cmax51.2±25.3 ng/ml, Tmax3.6±1.5 hr, Kel0.12±0.07 hr-1 and t½ 7.6±3.4 hr. Inter subject variations and race differences were shown in comparison with the published data in the literature.
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KEYWORD
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nicergoline, 10α-methoxy-9, 10-dihydrolysergol (MDL), bioavailability parameters, high performance liquid chromatography, mass spectrometry
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