Introduction: Macitentan is an endothelin receptor antagonist drug used in the treatment of
pulmonary arterial hypertension.
Materials and Methods: A new, sensitive, simple, accurate and rapid ultra-performance liquid chromatography
in combination with tandem triple quadruple mass spectrometry (UPLC-MS/MS) method has
been developed and validated for the determination of macitentan in pharmaceutical formulations. Macitentan
and bosentan which are used as internal standard (IS) were detected using atmospheric pressure
chemical ionization (APCI) in positive ion, multiple reaction monitoring (MRM) mode by monitoring
mass transitions (precursor to product) m/z 589.1→203.3 and 552.6→311.5, respectively. Chromatographic
separation was carried out on reverse phase C18 column (5 μm, 4.6 * 150 mm). Water containing
0.2 % acetic acid in acetonitrile (10:90, v/v) was used as the mobile phase in the isocratic elution.
The system was optimized with injection volume of 10 μL, column temperature of 35 °C and flow
rate of 1 mL min-1 Retention times were 1.97 min for macitentan and 1.72 min for IS.
Results and Conclusion: The calibration curve with a high correlation coefficient (0.9997) was linear
range 0.5-500 ng mL-1. The lower limit of quantitation (LLOQ) and average recovery values were determined
as 0.5 ng mL-1 and 99.7 %, respectively. The developed novel method has been successfully
applied for the determination of macitentan in pure form and pharmaceutical formulations.