Validation of LC-MS/MS methods for the determination of mirabegron and eight metabolites in human plasma in a paediatric population
| Autor: | Robert Huls, Walter Krauwinkel, Tom van den Berg, Cas van den Beld, Willem Niesing, John Meijer, Vincent Hofstede |
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| Rok vydání: | 2018 |
| Předmět: |
Male
Analyte Clinical Biochemistry Pharmaceutical Science Blood volume Adrenergic beta-3 Receptor Agonists 01 natural sciences Sensitivity and Specificity Analytical Chemistry Pharmacokinetics Tandem Mass Spectrometry Drug Discovery medicine Humans Solid phase extraction Child Spectroscopy Chromatography Dose-Response Relationship Drug 010405 organic chemistry Chemistry 010401 analytical chemistry Solid Phase Extraction Reproducibility of Results Assay sensitivity 0104 chemical sciences Thiazoles Human plasma Acetanilides Female Mirabegron medicine.drug Paediatric population Chromatography Liquid |
| Zdroj: | Journal of pharmaceutical and biomedical analysis. 167 |
| ISSN: | 1873-264X |
| Popis: | Mirabegron is the first registered β3-adrenoceptor agonist for treatment of overactive bladder as an alternative to antimuscarinics. Previously four liquid chromatography-tandem mass spectrometry assays were published to determine mirabegron and eight metabolites (M5, M8, M11–M16) in human plasma. In order to support paediatric development, the assays were further optimized to reduce the required blood volume and increase the sensitivity. The assays were miniaturized by using 96-well supported liquid extraction plates (mirabegron, M5, M16) or 96-well mixed-mode cation exchange solid phase extraction plates (M8, M11–M15) and a more sensitive MS-system was used. For the analytes, up to fivefold increase in assay sensitivity was achieved. The required blood sample volume was reduced from 10 to 2 mL for each timepoint. Validation demonstrated that the assays were accurate, precise and selective in the determination of mirabegron and metabolites. The assays were successfully applied to evaluate the pharmacokinetics of mirabegron in a paediatric population. |
| Databáze: | OpenAIRE |
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