Analysis of ifosfamide, 4-hydroxyifosfamide, N2-dechloroethylifosfamide, N3-dechloroethylifosfamide and iphosphoramide mustard in plasma by gas chromatography-mass spectrometry |
| |
| Authors: | Jeff J. -H. Wang Kenneth K. Chan |
| |
| Affiliation: | 1. School of Pharmacy, University of Southern California, Los Angeles, CA 90033, USA;2. Colleges of Pharmacy and Medicine, the Ohio State University, Columbus, OH 43210, USA;1. Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangdong, China;2. Lung Cancer Center, Shanghai Chest Hospital, affiliated to Shanghai JiaoTong University, Shanghai, China;3. Department of Oncology, Cancer Hospital of Jilin Province, Changchun, China;4. Department of Oncology, Shanghai Pulmonary Hospital, School of Medicine Tongji University Affiliated Cancer Institute, Shanghai, China;5. Department of Oncology, Peking Union Medical College Hospital, Beijing, China;6. Department of Oncology, 81st Hospital of the Chinese PLA, Nanjing, China;7. Department of Oncology, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China;8. Department of Oncology, the Second Hospital of Dalian Medical University, Dalian, China;9. Department of Chest Tumor, Beijing Chest Hospital, affiliated to Capital Medical University, Beijing, China;10. Cancer Hospital affiliated to Guangxi Medical University, Nanning, China;11. Asia Pacific Statistical Sciences, Lilly China Drug Development and Medical Affairs Center, Shanghai, China;12. Asia Pacific Statistical Sciences, Eli Lilly Australia, Sydney, Australia;13. Oncology, Lilly China Drug Development and Medical Affairs Center, Shanghai, China;14. Oncology Emerging Markets, Eli Lilly Interamérica Inc., Buenos Aires, Argentina;1. CIMA, Centre for Marine and Environmental Research, University of Algarve, Campus de Gambelas, 8000-139, Faro, Portugal;2. CBMR, Centre for Biomedical Research, University of Algarve, Campus de Gambelas, 8005-135, Faro, Portugal;1. Department of Chemistry, School of Chemical Engineering and Physical Sciences, Lovely Professional University, Phagwara, 144411, India;2. School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, 144411, India |
| |
| Abstract: | A sensitive and specific method for the simultaneous quantitation of ifosfamide (IF), 4-hydroxylifosfamide (4-OHIF), N2-dechloroethylifosfamide (N2D), N3-dechloroethylifosfamide (N3D) and iphosphoramide mustard (IPM) has been developed using gas chromatography-mass spectrometry (GC-MS) with an ion-trap mass spectrometer. Deuterium labeled analogues for each of these analytes were synthesized as the internal standards. The labile 4-OHIF in plasma was first converted to the more stable cyanohydrin adducts before dichloromethane extraction. IPM was extracted by C18 reversed-phase resin. All analytes were converted to their silyl derivatives before GC-MS analysis. The sensitivity limits ranged from 0.1 to 0.5 μg/ml when 100 μl of plasma was used. This method was validated with within-run coefficients of variation less than 5% (n=8) and between-run coefficients of variation less than 12% (n=6). The method was applied to the determination of plasma levels of IF and metabolites in the rat. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
