Liquid chromatography-tandem mass spectrometric assay for the light sensitive survivin suppressant sepantronium bromide (YM155) in mouse plasma
| Autor: | Rolf W. Sparidans, Jan J. Molenaar, Ilona J.M. den Hartog, M. Emmy M. Dolman, Jos H. Beijnen, Jan H.M. Schellens |
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| Přispěvatelé: | Oncology, Oncogenomics, Cancer Center Amsterdam |
| Rok vydání: | 2013 |
| Předmět: |
Bioanalysis
Electrospray Light Survivin Clinical Biochemistry Pharmaceutical Science Analytical Chemistry Inhibitor of Apoptosis Proteins chemistry.chemical_compound Mice Tandem Mass Spectrometry Drug Discovery Protein precipitation Animals Acetonitrile Spectroscopy Chromatography Elution Selected reaction monitoring Imidazoles Reproducibility of Results Dilution Triple quadrupole mass spectrometer Repressor Proteins chemistry Calibration Female Chromatography Liquid Naphthoquinones |
| Zdroj: | Journal of pharmaceutical and biomedical analysis, 92, 144-148. Elsevier |
| ISSN: | 1873-264X 0731-7085 |
| Popis: | A quantitative bioanalytical liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay for sepantronium bromide (YM155), an inhibitor of survivin, was developed and validated. Under reduced light exposure, plasma samples were pre-treated using protein precipitation with acetonitrile containing AT7519 as internal standard. After dilution with water, the extract was directly injected into the reversed-phase liquid chromatographic system. The eluate was transferred into the electrospray interface with positive ionization and compounds detected in the selected reaction monitoring mode of a triple quadrupole mass spectrometer. The assay was validated in a 0.5–100 ng/ml calibration range with r2 = 0.9981 ± 0.0007 using double logarithmic calibration (n = 5). Within day precisions (n = 6) were 3.6–8.8% and between day (3 days; n = 18) precisions 6.5–11.1%. Accuracies were between 92 and 111% for the whole calibration range. The light sensitive drug sepantronium was sufficiently stable under all relevant analytical conditions. Finally, the assay was successfully used to determine plasma drug levels in mice after administration of sepantronium bromide by continuous infusion from subcutaneously implanted osmotic pumps. |
| Databáze: | OpenAIRE |
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