Simultaneous quantification of ambrisentan, macitentan and sitaxentan in human plasma using UPLC–MS/MS. (19th January 2020)

• Record Type: Journal Article
• Authors: van de Velde, Daan; Bahmany, Soma; Hitzerd, Emilie; van Domburg, Bart; Versmissen, Jorie; Danser, A.H. Jan; Koch, Birgit C.P.
• Is Part Of: Biomedical chromatography. Volume 34:Number 3(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-01-19
• Subjects: endothelin receptor antagonists -- multi‐method -- protein precipitation -- UPLC–MS/MS; Chromatographic analysis -- Periodicals; Biology -- Periodicals; Medicine -- Periodicals; Biology -- Periodicals; Chromatography -- methods -- Periodicals; Medicine -- Periodicals; 543.089
• DOI: 10.1002/bmc.4787
• Languages: English
• ISSNs: 0269-3879

Abstract

Abstract: 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.