Development and validation of LC-MS/MS methods for the determination of mirabegron and its metabolites in human plasma and their application to a clinical pharmacokinetic study
| Autor: | Raymond van Teijlingen, Shin Takusagawa, Takashi Usui, Marcel van Gelderen, Cas van den Beld, John Meijer |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Bioanalysis Electrospray ionization Metabolite Clinical Biochemistry Atmospheric-pressure chemical ionization Tandem mass spectrometry Mass spectrometry Biochemistry Sensitivity and Specificity Analytical Chemistry Matrix (chemical analysis) chemistry.chemical_compound Drug Stability Tandem Mass Spectrometry medicine Humans Chromatography High Pressure Liquid Chromatography Chemistry Reproducibility of Results Cell Biology General Medicine Thiazoles Linear Models Acetanilides Mirabegron medicine.drug |
| Zdroj: | Journal of chromatography. B, Analytical technologies in the biomedical and life sciences. |
| ISSN: | 1873-376X |
| Popis: | Mirabegron is being developed for the treatment of overactive bladder. To support the development of mirabegron, including pharmacokinetic studies, liquid chromatography/tandem mass spectrometry methods for mirabegron and eight metabolites (M5, M8, M11-M16) were developed and validated for heparinized human plasma containing sodium fluoride. Four separate bioanalytical methods were developed for the analysis of: (1) mirabegron; (2) M5 and M16; (3) M8; and (4) M11-M15. Either solid-phase extraction or liquid-liquid extraction was used to extract the analytes of interest from matrix constituents. For mirabegron, an Inertsil C₈-3 analytical column was used and detection was performed using a triple-quad mass spectrometer equipped with an atmospheric pressure chemical ionization interface. For the metabolite assays, chromatographic separation was performed through a Phenomenex Synergi Fusion-RP C₁₈ analytical column and detection was performed using a triple-quad mass spectrometer equipped with a Heated Electrospray Ionization interface. The validation results demonstrated that the developed liquid chromatography/tandem mass spectrometry methods were precise, accurate, and selective for the determination of mirabegron and its metabolites in human plasma. All methods were successfully applied in evaluating the pharmacokinetic parameters of mirabegron and metabolites in human plasma. |
| Databáze: | OpenAIRE |
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