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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Ding, Yi Lu, ChengTao Yang, Jing Jin, Xin Yang, Lin Wang, Chao Ma, ZongYing Zhu, YanRong Ding, LiKun Jia, YanYan Wen, AiDong |
| Description | Country affiliation: China Author Affiliation: Ding Y ( Department of Pharmacy, Xijing Hospital of the Fourth Military Medical University, 17 Changlexi Street, Xi'an 710032, Shanxi, China.) |
| Abstract | Felotaxel (SHR110008), currently under clinical investigation in phase I trial, is a new effective taxane with greater anticancer activity and less toxicity than docetaxel. Pharmacokinetic studies in animal models are the important components in clinical development of this agent. In this study, a rapid and sensitive analytical method based on high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for the determination of felotaxel in tumor-bearing mice plasma, urine, feces and tissues (brain, heart, liver, lung and kidney and tumor). For all matrices, sample preparation involved liquid-liquid extraction with ethyl acetate. Calibration curves (1/x² weighted) offered satisfactory linearity (r² ≥ 0.995) within the test range. The lower limit of quantitation (LLOQ) for all matrices was 10 ng/ml except that for mouse plasma and brain LLOQ was 1 ng/ml. The accuracy and precision ranged from 86.1 to 107.2% and 1.1 to 9.2%, respectively. Recoveries (73.9-96.1%) and matrix effects (76.4-97.2%) were satisfactory in all the biological matrices examined. Stability studies (85.1-101.5%) showed that felotaxel was stable both during the assay procedure and long-term storage. The assay was successfully applied to plasma pharmacokinetics, tissue distribution and excretion study of mice. The pharmacokinetic parameters, such as half-life, mean residence time, maximum concentration were determined. The preclinical data are useful for the design of clinical trials of felotaxel. |
| File Format | HTM / HTML |
| ISSN | 15700232 |
| Volume Number | 887-888 |
| e-ISSN | 1873376X |
| Journal | Journal of Chromatography B |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2012-03-01 |
| Publisher Place | Netherlands |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Analytical Chemistry Antineoplastic Agents Pharmacokinetics Chromatography, Liquid Methods Lung Neoplasms Metabolism Tandem Mass Spectrometry Taxoids Animals Analysis Chemistry Diazepam Drug Stability Drug Therapy Male Mice Mice, Nude Reproducibility Of Results Sensitivity And Specificity Tissue Distribution Xenograft Model Antitumor Assays Journal Article Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine Analytical Chemistry Clinical Biochemistry Biochemistry |
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