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Separation and Characterization of New Forced Degradation Products of Macitentan: A Dual Endothelin Receptor Antagonist

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Abstract

Macitentan (MCT) is an endothelin receptor antagonist used for the treatment of pulmonary arterial hypertension. In the present study, MCT was subjected to forced degradation as per ICH guidelines. The drug degraded extensively in acidic, basic as well as neutral hydrolytic conditions and seven degradation products (DPs) were formed. All these DPs were selectively separated using high-performance liquid chromatography (HPLC) with a stationary phase of Inertsil C18 column (150 × 4.6 mm, 5 μm) and a mobile phase consisting of gradient mixture of 0.02% trifluoroacetic acid (TFA) and acetonitrile (ACN). The developed HPLC method was transferred to LC–ESI–QTOF–MS/MS for identification of DPs. The final mass spectrometric conditions were optimized for better ionization of drug and DPs with optimum mass signal sensitivity. All the formed DPs were new and well separated with sufficient resolution. The developed HPLC method was validated as per ICH-guidelines and can be used in drug testing labs for determination of quality of MCT in bulk and finished formulations.

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Acknowledgements

The authors would like to show appreciation towards the National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, and the Ministry of Chemicals and Fertilizers, New Delhi, India, for providing a facilities and research fellowship.

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Authors and Affiliations

  1. Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, 500037, India

    Mohit Thummar, Debasish Swain & S. Gananadhamu

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  1. Mohit Thummar
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  2. Debasish Swain
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  3. S. Gananadhamu
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Correspondence to S. Gananadhamu.

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Authors Mohit Thummar, Debasish Swain and Dr. S. Gananadhamu have declared that they have no conflict of interest.

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Thummar, M., Swain, D. & Gananadhamu, S. Separation and Characterization of New Forced Degradation Products of Macitentan: A Dual Endothelin Receptor Antagonist. Chromatographia 81, 525–531 (2018). https://doi.org/10.1007/s10337-018-3471-y

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  • DOI: https://doi.org/10.1007/s10337-018-3471-y

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