Determination of S-1 (combined drug of tegafur, 5-chloro-2,4- dihydroxypyridine and potassium oxonate and 5-fluorouracil in human plasma and urine using high-performance liquid chromatography and gas chromatography-negative ion chemical ionization mass spectrometry |
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| Institution: | 1. Chemistry Department, Sharif University of Technology, P.O. Box 11155-3516, Tehran, Iran;2. Chemistry Department, University of Bath, Bath, BA2 7AY, UK;3. Green SOC – Dipartimento di Chimica Biologia e Biotecnologie, Università degli Studi di Perugia, I-06123, Perugia, Italy;1. Laboratory for Climate Studies & CMA-NJU Joint Laboratory for Climate Prediction Studies, National Climate Center, China Meteorological Administration, Beijing, China;2. State Key Laboratory of Severe Weather, Chinese Academy of Meteorological Sciences, Beijing, China;3. Collaborative Innovation Center on Forecast and Evaluation of Meteorological Disasters, Nanjing University of Information Science & Technology, Nanjing, China;4. National Centre for Atmospheric Science and Department of Meteorology, University of Reading, Reading, UK;1. Institute of Neuropathology, University Hospital of Bellvitge, IDIBELL (Biomedical Research Institute of Bellvitge), Carrer Feixa Llarga sn, 08907 Hospitalet de Llobregat, Spain;2. Proteomics Platform, Barcelona Science Park, 08028 Barcelona, Spain;3. Department of Experimental Medicine, University of Lleida-Biomedical Research Institute of Lleida, 25198 Lleida, Spain;4. Department of Pathology and Experimental Therapeutics, University of Barcelona, Carrer Feixa Llarga sn, 08907 Hospitalet de Llobregat, Spain;5. CIBERNED (Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas), Spain;1. Univ. Lille, Inserm, U995—LIRIC—Lille Inflammation Research International Center, F-59000 Lille, France;2. Ecole des Hautes Etudes d’Ingénieur (HEI), Laboratoire de Pharmacochimie, 13 rue de Toul, F-59046 Lille, France;3. ‘Alexandru Ioan Cuza’ University of Iasi, Faculty of Chemistry, Bd. Carol I nr. 11, 700506 Iasi, Romania;4. UFR Pharmacie, Laboratoire de Chimie Analytique, BP 83, F-59006 Lille, France |
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| Abstract: | A high-performance liquid chromatography (HPLC) and gas chromatography-negative ion chemical ionization mass spectrometry (GC-NICI-MS) method was developed for the analysis of the combined antitumor drug S-1 (tegafur, 5-chloro-2,4-dihydroxypyridine and potassium oxonate and active metabolite 5-fluorouracil in human plasma and urine. Tegafur was fractionated from biological fluids by extraction with dichloromethane and analyzed by HPLC. 5-Fluorouracil and 5-chloro-2,4-dihydroxypyridine were extracted with ethyl acetate from the residual layer after extraction of tegafur, and converted to pentafluorobenzyl (PFB) derivatives. Potassium oxonate was cleaned up with an anion-exchange column (Bond Elut NH2). The extracted potassium oxonate was degraded to 5-azauracil and converted to PFB derivatives. The PFB derivatives were analyzed by GC-NICI-MS. A stable isotope was employed as the internal standard in the GC-NICI-MS analysis. The limits of quantitation of tegafur, 5-fluorouracil, 5-chloro-2,4-dihydroxypyridine and potassium oxonate in plasma were 10, 1, 2 and 1 ng/ml, respectively. The reproducibility of the analytical method according to the statistical coefficients is ∼10%. The accuracy of the method is good; that is, the relative error is <10%. The methods were applied to pharmacokinetic studies of S-1 in patients. |
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