Preparative Isolation and High-Resolution Mass Identification of 10 Stressed Study Degradants of Nicorandil Tablets

Abstract

Nicorandil is a potent drug with a dual mechanism of action which results in its wide application in treating angina patients. Since the literature review showed no single preparative method for isolation and liquid chromatography-mass spectrometry (LC-MS) compatible [high-performance liquid chromatography (HPLC) or ultra performance liquid chromatography (UPLC)] method for identification for the impurities generated in process and by force degradation was reported. Thus an attempt was made to develop a single preparative method for isolation and HPLC and UPLC methods for identification of impurities of nicorandil in tablet dosage form. Ten degradants were found in the formulated drug under the stress conditions, [40°C/75% relative humidity for 2 months] in an LC-MS compatible method. A cost effective and high-throughput simple gradient preparative HPLC method was developed with a runtime of 30 min to isolate all the degradants. The method is capable and can be used to isolate further degradants. To detect these degradants, rapid and effecient HPLC and UPLC methods were developed and the same were identified by UPLC-time of flight mass spectrometry (TOF MS). The crux of this work involves a single preparative isolation method and UPLC identification method for all degradants with a very short runtime, i.e., 13.8 min, and, furthermore, the method has the potential to separate a wide range of degradants.