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- Title
Determination of 2-(3-Benzoyl)-4-Hydroxy-1,1-Dioxo-2H-1,2-Benzothiazine-2-yl-1-Phenylethanone by Liquid Chromatography–Tandem Mass Spectrometry.
- Authors
Zheng, Zhi; Song, Jin Sook; Lee, Byung Hoi; Ahn, Sung-Hoon; Ahn, Jin-Hee; Woo, JaeChun; Park, Ji-Young; Yoo, Dae Seok; Bae, Myung Ae
- Abstract
2-(3-Benzoyl)-4-hydroxy-1,1-dioxo-2H-1,2-benzothiazine-2-yl-1-phenylethanone (KR-66344), a 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor, is newly developed for the control of type 2 diabetes mellitus (T2DM) and metabolic syndrome. A method for the determination of KR-66344 in rat plasma was developed by liquid chromatography–electrospray ionization tandem mass spectrometry (LC–ESI-MS-MS) to evaluate the pharmacokinetics of KR-66344. Plasma samples were processed by a liquid–liquid extraction method with ethyl acetate and introduced onto the LC–MS-MS system. The analyte and imipramine (internal standard) were analyzed by multiple reaction monitoring based on transitions at m/z 420.1 → 105.0 and 282.2 → 86.0, respectively. The calibration curve was linear (r = 0.9993) over the concentration range of 1.0–1,000 ng/mL. The mean recovery values for KR-66344 and imipramine were 83.8 and 86.2%, respectively. The mean inter-day and intra-day assay precision values were 3.9 and 2.4%, respectively. KR-66344 was stable under various handling and storage conditions. This developed method was applied to a pharmacokinetic study after the oral administration of KR-66344 in rats. The concentration of KR-66344 was readily measurable in rat plasma up to 24 h post-dose after an oral administration, suggesting that current assay is applicable to pharmacokinetic studies for KR-66344.
- Subjects
HYDROXYSTEROID dehydrogenases; TYPE 2 diabetes; METABOLIC syndrome; PHARMACOKINETICS; IMIPRAMINE; LIQUID chromatography-mass spectrometry
- Publication
Journal of Chromatographic Science, 2014, Vol 52, Issue 5, p406
- ISSN
0021-9665
- Publication type
Article
- DOI
10.1093/chromsci/bmt050