title: Simultaneous quantification of 22R and 22S epimers of budesonide in human plasma by ultra-high-performance liquid chromatography-tandem mass spectrometry: application in a stereoselective pharmacokinetic study.
abstract: Budesonide (BUD) is used as a mixture of 22R and 22S epimers for the topical treatment of asthma, rhinitis, and inflammatory bowel disease. To study stereoselectivity in the pharmacokinetics of each epimer, we developed a stereoselective and sensitive ultra-high-performance liquid chromatography-tandem mass spectrometry method for the quantitative determination of 22R and 22S epimers of BUD in human plasma. The epimers of BUD were extracted from plasma using n-hexane/dichloromethane/isopropanol (2:1:0.1, v/v/v) under alkaline conditions. Baseline separation was obtained within 7min on an Acquity UPLC BEH C18 (50mm×2.1mm, 1.7μm) column using an isocratic mobile phase consisting of acetonitrile/5mM ammonium acetate/acetic acid (29:71:0.142, v/v/v) at a flow rate of 0.7mL/min. Mass spectrometric detection was performed in a multiple reaction monitoring mode using the m/z 489→357 transition for BUD epimers and the m/z 497→357 transition for the internal standard d8-BUD epimers. Calibration curves were linear over the concentration ranges of 5.0-500 and 5.0-3000pg/mL for 22R-BUD and 22S-BUD, respectively. The lower limit of quantification was 5.0pg/mL for both epimers. The method was successfully applied in a pharmacokinetic study of BUD controlled-release capsules in humans. Consistent differences in the pharmacokinetics of the 22R and 22S epimers were observed, the AUC(0-∞) of 22S-BUD was approximately six times higher than that of 22R-BUD, and the 22S-/22R-BUD ratio of total body clearance was 0.17.
authors: Zhejiang University of Technology, Hangzhou 310014, PR China.
authors: Youming
authors: Y
authors: Lu
authors: Zuoming
authors: Z
authors: Sun
authors: Yifan
authors: Y
authors: Zhang
authors: Xiaoyan
authors: X
authors: Chen
authors: Dafang
authors: D
authors: Zhong
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000097:blood* / Q000737:chemistry; D019819:Budesonide / Q000097:blood* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005260:Female; D005938:Glucocorticoids / Q000097:blood* / Q000737:chemistry; D006801:Humans; D008297:Male; D012680:Sensitivity and Specificity; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D019819:Budesonide