IJSRST1731024 | 02Nov 2017 | Accepted:30Dec2017 | November-December - 2017 [(3)10 : 105-117] © 2017 IJSRST | Volume 3 | Issue 10 | Print ISSN: 2395-6011 | Online ISSN: 2395-602X National Conference on Research and Developments in Synthetic Organic Chemistry 105 Development and Validation of Stability Indicating RP-HPLC Method on Core Shell Columnfor Determination of Degradation and Process Related Impurities of Macitentan- Anti-hypertension Drug Shashikant B. Landge 1 , Sanjay A. Jadhav 1 , Sunil B. Dahale 1 ,Rajendra S. Shinde 1 , Kunal M. Jagtap 1 , Saroj R. Bembalkar 2 , Vijayavitthal T. Mathad 1* 1 Department of Process Research and Development, Megafine Pharma Lakhmapur, Dindori, Nashik, Maharashtra, India 2 Department of Chemistry, Deogiri College, Aurangabad, Maharashtra, India ABSTRACT A core shell chromatographic column was used to separate the nine process related and degradation related impurities(Imp-1 to Imp-9) of Macitentanis described in this article. The chromatographic separation was achieved on a Sigma-Aldrich‟s „Ascentis Express ® C18 (4.6 mm x 100 mm, 2.7 µ)‟ HPLC column with a runtime of 35 min. Forced degradation study was carried out under acidic, alkaline, oxidative, photolytic, and thermal degradation conditionsto demonstrate the stability-indicating nature of developed RP-HPLC method.The methodology consists of mobile phase-A as aphosphate buffer and mobile phase-B as a mixture of acetonitrile andmethanol. The column oven temperature was set at 45°C, injection thermostat was set at 5°C, and photodiode array detector (PDA) was set at 215 nm.Adeveloped method was validated as per ICH guideline and found rapid, specific,precise, sensitive,androbust. The proposed RP-HPLC method was successfully applied to the analysis of drug substance and drug product of Macitentan. Keywords: Macitentan, Core-Shell HPLC Column, RSD and Validation, Stability Indicating. I. INTRODUCTION Macitentan is an antagonist drug chemically known as N-[5-(4-Bromophenyl)-6-[2-[(5-bromo-2- pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]- N'propylsulfamide and sold under the brand name “Opsumit” to treat the people with pulmonary arterial hypertension (PAH), a chronic, life-threatening disorder which severely compromises the function of the lungs and heart. It is an endothelin receptor antagonist (ERA) approved for the treatment of pulmonary arterial hypertension (PAH). Macitentan is a dual ERA, meaning that it acts as an antagonist of two endothelin (ET) receptor subtypes, ETA and ETB[1].However, Macitentan has a 50-fold increased selectivity for the ETA subtype compared to the ETBsubtype [2].The drug received approval from the U.S. Food and Drug Administration (FDA) on October 13, 2013[3]. An analytical method development to determine the quality of product is a critical task during the synthesis of product in generic companies because there is continuous improvement in the process by usingnew reagents, intermediates or by changing the route of synthesis. To develop the robust and selective analytical method nine process related impurities have been discovered during the synthesis of product by process development laboratory (Imp-1 to Imp-9)(Figure1).