Validation of high-performance liquid chromatography–tandem mass spectrometry assays quantifying omacetaxine mepesuccinate and its 4′‑des-methyl and cephalotaxine metabolites in human plasma and urine
| Autor: | Nijenhuis, C. M., Lucas, L., Rosing, H., Schellens, J. H M, Beijnen, J. H., Gorman, S. H., Burke, S. M., Campbell, D. A., Chapple, M. W., Yousey, T. H., Mulvana, D. E., Pharmacoepidemiology and Clinical Pharmacology, Sub Clinical Pharmacology |
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| Přispěvatelé: | Pharmacoepidemiology and Clinical Pharmacology, Sub Clinical Pharmacology |
| Rok vydání: | 2015 |
| Předmět: |
Harringtonines
4'-Des-methylhomoharringtonine GLP Clinical Biochemistry Mass spectrometry Tandem mass spectrometry Biochemistry High-performance liquid chromatography Analytical Chemistry chemistry.chemical_compound Cephalotaxine Limit of Detection Tandem Mass Spectrometry Omacetaxine mepesuccinate Humans Protein precipitation Chromatography High Pressure Liquid Detection limit Chromatography HPLC-MS/MS Chemistry Cell Biology General Medicine Antineoplastic Agents Phytogenic Triple quadrupole mass spectrometer Homoharringtonine Esterase inhibitor |
| Zdroj: | Journal of chromatography. B, 1002, 152. Elsevier |
| ISSN: | 1570-0232 |
| DOI: | 10.1016/j.jchromb.2015.08.015 |
| Popis: | Omacetaxine mepesuccinate (hereafter called omacetaxine) is a modified cephalotaxine and is registered (Synribo®) for the treatment of adult patients with chronic myeloid leukemia (CML) with resistance and/or intolerance to two or more tyrosine kinase inhibitors (TKIs). To evaluate the pharmacokinetics of omacetaxine, sensitive high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays for the quantification of omacetaxine and its inactive 4'-des-methyl (4'-DMHHT) and cephalotaxine metabolites in human plasma and urine were developed and validated.Since omacetaxine is mainly metabolised by esterases, the plasma samples were immediately stabilised after collection with an esterase inhibitor and stored at a nominal temperature of -80. °C. Urine samples were stored at -80. °C immediately after collection. Protein precipitation was applied as the sample pretreatment method for the plasma samples, and urine samples were processed using solid-phase extraction (SPE). For both assays, the dried and reconstituted extracts were injected on a XBridge BEH Phenyl column for analysis of all analytes. Gradient elution was applied with 0.1% formic acid in water and methanol as mobile phases. Analytes were ionised using a turbospray ionisation source in positive mode and detected with a triple quadrupole mass spectrometer.The validated plasma assay quantifies all analytes in the concentration range of 0.1-100. ng/mL and the urine assay in the range of 0.1-50. ng/mL. At all concentrations, the accuracies were within ±15% of the nominal concentrations and precisions were ≤15%. The developed methods have successfully been applied in a human mass balance study of omacetaxine. |
| Databáze: | OpenAIRE |
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