Stereoselective analysis of bupropion and hydroxybupropion in human plasma and urine by LC/MS/MS

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• 作者：Rebecka Coles ; Evan D. Kharasch
• 关键词：Bupropion ; Hydroxybupropion ; Mass spectrometry ; Chiral analysis ; LC– ; MS– ; MS
• 刊名：Journal of Chromatography B, Analytical Technologies in the Biomedical and Life Sciences
• 出版年：2007
• 出版时间：15 September 2007
• 年：2007
• 卷：857
• 期：1
• 页码：67-75
• 全文大小：662 K

文摘

A sensitive, stereoselective assay using solid phase extraction and LC–MS–MS was developed and validated for the analysis of (R)- and (S)-bupropion and its major metabolite (R,R)- and (S,S)-hydroxybupropion in human plasma and urine. Plasma or glucuronidase-hydrolyzed urine was acidified, then extracted using a Waters Oasis MCX solid phase 96-well plate. HPLC separation used an α₁-acid glycoprotein column, a gradient mobile phase of methanol and aqueous ammonium formate, and analytes were detected by electrospray ionization and multiple reaction monitoring with an API 4000 Qtrap. The assay was linear in plasma from 0.5 to 200 ng/ml and 2.5 to 1000 ng/ml in each bupropion and hydroxybupropion enantiomer, respectively. The assay was linear in urine from 5 to 2000 ng/ml and 25 to 10,000 ng/ml in each bupropion and hydroxybupropion enantiomer, respectively. Intra- and inter-day accuracy was >98 % and intra- and inter-day coefficients of variations were less than 10 % for all analytes and concentrations. The assay was applied to a subject dosed with racemic bupropion. The predominant enantiomers in both urine and plasma were (R)-bupropion and (R,R)-hydroxybupropion. This is the first LC–MS/MS assay to analyze the enantiomers of both bupropion and hydroxybupropion in plasma and urine.