کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1212993 1494117 2013 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Quantitative determination of capecitabine and its six metabolites in human plasma using liquid chromatography coupled to electrospray tandem mass spectrometry
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
Quantitative determination of capecitabine and its six metabolites in human plasma using liquid chromatography coupled to electrospray tandem mass spectrometry
چکیده انگلیسی

Capecitabine is the oral prodrug of the anticancer drug 5-fluorouracil (5-FU). The purpose of this study was to quantify capecitabine and its metabolites including 5′-deoxy-5-fluorocytidine (5′-dFCR), 5′-deoxy-5-fluorouridine (5′-dFUR), 5-FU, dihydro-5-fluorouracil (FUH2), α-fluoro-ureidopropionic acid (FUPA) and fluoro-β-alanine (FBAL) in human plasma using liquid chromatography coupled to electrospray tandem mass spectrometry. To this end two individual assays were developed: one for the simultaneous quantification of capecitabine, 5′-dFCR and 5′-dFUR using reversed phase chromatography and gradient elution, and one assay for 5-FU, FUH2, FUPA and FBAL using hydrophilic interaction chromatography and isocratic elution. Both assays were fully validated according to current FDA guidelines. Total run time for the capecitabine assay was 9.0 min, and of the 5-FU assay 5.0 min. Analyte extraction was performed by protein precipitation. Stable labeled isotopes for each of the analytes were used as internal standards. The linear ranges of the analytes were 50–6000 ng/mL for the capecitabine assay and 50–5000 ng/mL for the 5-FU assay. Validation results demonstrate that capecitabine and its metabolites can be rapidly, accurately, precisely and robustly quantified in human plasma with the presented methods. Both assays are currently in extensive use in support of pharmacokinetic studies in patients treated with capecitabine or 5-FU.


► Simultaneous quantification of capecitabine and all its six metabolites in plasma.
► Assay fully validated according to current FDA guidelines.
► Rapid, robust, selective and sensitive method using HPLC–tandem mass spectrometry.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Chromatography B - Volumes 913–914, 15 January 2013, Pages 30–40
نویسندگان
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