Simultaneous quantification of ambrisentan, macitentan and sitaxentan in human plasma using UPLC–MS/MS
| Autor: | A.H. Jan Danser, Emilie Hitzerd, Jorie Versmissen, Soma Bahmany, Daan van de Velde, Bart van Domburg, Birgit C. P. Koch |
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| Přispěvatelé: | Pharmacy, Internal Medicine |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Ambrisentan
Clinical Biochemistry Thiophenes Sensitivity and Specificity 030226 pharmacology & pharmacy 01 natural sciences Biochemistry Analytical Chemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pharmacokinetics Tandem Mass Spectrometry Liquid chromatography–mass spectrometry Drug Discovery Sitaxentan medicine Humans Protein precipitation Molecular Biology Antihypertensive Agents Chromatography High Pressure Liquid Macitentan Pharmacology Sulfonamides Chromatography Phenylpropionates 010401 analytical chemistry Selected reaction monitoring Reproducibility of Results Isoxazoles General Medicine 0104 chemical sciences Pyridazines Pyrimidines chemistry Linear Models Endothelin receptor medicine.drug |
| Zdroj: | Biomedical Chromatography, 34. John Wiley & Sons Ltd. |
| ISSN: | 0269-3879 |
| Popis: | Endothelin receptor antagonists (ERAs) such as, ambrisentan, macitentan and sitaxentan are primarily used for the treatment of pulmonary arterial hypertension. Considering the rise in endothelin in pre-eclampsia, ERAs may also be useful in its treatment. To evaluate the pharmacokinetics of ERAs, a rapid ultra-performance liquid chromatography tandem mass spectrometry method was developed and validated to determine the concentration of ambrisentan, macitentan and sitaxentan in human plasma. Plasma samples were treated with methanol to induce protein precipitation. A chromatographic separation was performed on a C18 column using a gradient of methanol-water containing 0.1% formic acid and 0.013% ammonium acetate and a flow rate of 0.5 ml/min. Multiple reaction monitoring was used for quantification. This method was validated in a linear range of 20.28-2028 μg/l for ambrisentan, 4.052-405.2 μg/l for macitentan and 205.4-10 270 μg/l for sitaxentan. The method was successfully validated according to US Food and Drug Administration guidelines to determine the concentrations of macitentan, ambrisentan and sitaxentan in human plasma. This method is now being used for study samples and clinical patient samples. |
| Databáze: | OpenAIRE |
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