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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Sparidans, Rolf W. Tang, Seng Chuan Nguyen, Luan N. Schinkel, Alfred H. Schellens, Jan H. M. Beijnen, Jos H. |
| Description | Country affiliation: Netherlands Author Affiliation: Sparidans RW ( Utrecht University, Faculty of Science, Department of Pharmaceutical Sciences, Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht, The Netherlands. R.W.Sparidans@uu.nl) |
| Abstract | A quantitative bioanalytical liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay for the ALK inhibitor crizotinib was developed and validated. Plasma samples were pre-treated using protein precipitation with acetonitrile containing crizotinib-(13)C(2)-(2)H(5) as internal standard. The extract was directly injected into the chromatographic system after dilution with water. This system consisted of a sub-2 µm particle, trifunctional bonded octadecyl silica column with a gradient using 0.1% (v/v) of ammonium hydroxide in water and methanol. The eluate was transferred into the electrospray interface with positive ionization and the analyte was detected in the selected reaction monitoring mode of a triple quadrupole mass spectrometer. The assay was validated in a 10-10,000 ng/ml calibration range with r(2)=0.99980±0.00014 for double logarithmic linear regression (n=5). Within day precisions (n=6) were 3.4-4.8%, between day (3 days; n=18) precisions 3.6-4.9%. Accuracies were between 107% and 112% for the whole calibration range. The drug was sufficiently stable under all relevant analytical conditions. Oxidative metabolites of crizotinib were monitored semi-quantitatively. Finally, the assay was successfully used to assess drug pharmacokinetics in mice. |
| File Format | HTM / HTML |
| ISSN | 15700232 |
| Volume Number | 905 |
| e-ISSN | 1873376X |
| Journal | Journal of Chromatography B |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2012-09-15 |
| Publisher Place | Netherlands |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Analytical Chemistry Chromatography, Liquid Methods Pyrazoles Blood Pyridines Tandem Mass Spectrometry Animals Drug Stability Linear Models Male Mice Chemistry Pharmacokinetics Reproducibility Of Results Sensitivity And Specificity Journal Article |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine Analytical Chemistry Clinical Biochemistry Biochemistry |
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