Telithromycin の体液内測定法に関する研究
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概要
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In order to study on human pharmacokinetics of telithromycin (TEL), sensitive bioassay method, HPLC method and LC/MS/MS method were developed and the validation studies of these analytic methods were carried out. As the bioassay method, agar-well diffusion method was developed using <I>Micrococcus luteus</I> ATCC 9341, have high sensitivity and high specificity, as a test organism and Heart infusion agar (pH 9.0) as a test medium. The validation studies on the bioassay method resulted in good accuracy and reliability in the range of 0.002-0.032μg eq/mL in human plasma and urine samples. The lower limit of quantification were 0.002 and 0.004μg eq/mL for plasma and urine. In HPLC method, plasma samples were deproteinated by addition of acetonitrile and reconstituted in mobile phase, and urine samples was diluted directly in mobile phase composition. These mixtures were chromatographed in reverse phase conditions and detected by fluorimetry at 263 nm (excitation wavelength) and 460 nm (emission wavelength). The limit of quantification was 0.005μg/mL for a 300μL aliquot of human plasma and 0.5, u g/mL for a 50, μL aliquot of human urine, respectively. The usable range of concentrations used for the calibration was 0.005 to 1.0μg/mL in plasma and 0.5 to 100μg/mL in urine. As LC/MS/MS method, APCI ionization method was employed, and mass spectrometry was conducted after separation by HPLC under reverse phase conditions. The usable range of concentrations used for the calibration was 5 to 3, 000 ng/mL for a 50μL aliquot of human plasma and the limit of quantification was 5 ng/mL. The validation studies on these methods revealed good accuracy and reliability. The results of stability studies on TEL in clinical samples, showed that blood samples can be stored at room temperature or at 4°C for a maximum of 4 hours following collection. Plasma samples and urine samples containing TEL in clinical studies can be stored at about-20°C for 12 months and at about-25°Cc for 6 months, respectively.
- 公益社団法人 日本化学療法学会の論文
- 2003-09-30
著者
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山崎 浩子
アベンティスファーマ株式会社研究開発本部開発研究所薬物動態研究室
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鈴木 恵美
アベンティスファーマ株式会社研究開発本部開発研究所薬物動態研究室
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DUPRONT A
Department of Drug Metabolism and Pharmacokinetics, Aventis Pharma
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COUSSEDIERE D
Department of Drug Metabolism and Pharmacokinetics, Aventis Pharma
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土田 晃敬
アベンティスファーマ株式会社研究開発本部開発研究所薬物動態研究室
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小幡 淳雄
アベンティスファーマ株式会社研究開発本部開発研究所薬物動態研究室
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三浦 公道
株式会社三菱化学ビーシーエル治験研究部薬物動態グループ
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Pascual M
Department Of Pharmacokinetics Aventis Pharma
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Coussediere D
Department Of Pharmacokinetics Aventis Pharma
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