Development and validation of an LC-MS/MS method with a broad linear dynamic range for the quantification of tivozanib in human and mouse plasma, mouse tissue homogenates, and culture medium
| Autor: | Bruin, M A C, Rosing, H, Lucas, L, Wang, J, Huitema, A D R, Schinkel, A H, Beijnen, J H, Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology |
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| Přispěvatelé: | Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Bioanalysis
Tivozanib Formic acid Clinical Biochemistry Mass spectrometry Kidney Linear dynamic range 030226 pharmacology & pharmacy 01 natural sciences High-performance liquid chromatography Biochemistry Analytical Chemistry 03 medical and health sciences chemistry.chemical_compound Mice Plasma 0302 clinical medicine Tandem Mass Spectrometry medicine Protein precipitation Animals Humans Isotopologue LC-MS/MS Lung Chromatography High Pressure Liquid Chromatography Chemistry Phenylurea Compounds 010401 analytical chemistry Selected reaction monitoring General Medicine Cell Biology 0104 chemical sciences Culture Media Liver Quinolines Spleen medicine.drug |
| Zdroj: | Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 1125. Elsevier Journal of Chromatography B, 1125. Elsevier |
| ISSN: | 1570-0232 |
| Popis: | The first bioanalytical assay for tivozanib in human and mouse plasma, mouse tissue homogenates and culture medium was developed and validated over a linear dynamic range from 0.5 to 5000 ng/mL. The extended concentration range will cover the quantification of tivozanib in the majority of study samples, reducing the need for reanalysis which is often not possible due to limited amount of sample in preclinical studies. A simple and fast pretreatment method was used consisting of protein precipitation with acetonitrile followed by dilution of the supernatant. The final extract was injected onto an Ultra-Performance Liquid Chromatography (UPLC) BEH C18 column with gradient elution of formic acid in water and formic acid in acetonitrile mobile phase. Chromatographic separation was followed by detection with a triple-quadrupole mass spectrometer operating in the positive ion-mode. By simultaneously monitoring the sensitive conventional [M + H]+ isotopologue- product transition for quantification of low concentrations and a less abundant [M + H]++1 isotopologue- product transition to reduce the sensitivity for quantification of high concentrations, we were able to extend the overall linear dynamic range up to 0.5-5000 ng/mL. A full validation was performed in human plasma and a partial validation was executed for the other matrices. All results were within the acceptance criteria of the European Medicines Agency (EMA) guidelines and the US Food and Drug Administration (FDA) guidance, except for the carry-over. This was solved by the analysis of extra matrix blanks and by grouping study samples containing a high tivozanib concentration in the sample sequence. In this way carry-over did not impact the data integrity. We demonstrated that by measuring two multiple reaction monitoring (MRM) transitions for tivozanib, the linear dynamic range could be extended from two to four decades. The assay was successfully applied in pharmacokinetic studies in mice and a transport assay. |
| Databáze: | OpenAIRE |
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