Forced Degradation Profiling of Cilnidipine: A Multi-technique Characterisation using UHPLC–MS, HRMS, Prep-HPLC, and NMR

Abstract

Currently, no forced degradation studies for Cilnidipine are available. Therefore, it is essential to monitor its stability under various conditions. The main medical disorders that Cilnidipine is used to treat are hypertension, which is high blood pressure, and angina, also known as chest discomfort. Cilnidipine underwent forced degradation experiments, and sample analysis was performed by liquid chromatography-mass spectrometry (LC–MS). As per regulatory guidelines, the sample was subjected to hydrolytic, oxidative, thermal, and photolytic stress conditions. The drug remained stable when exposed to oxidative, thermal, and photolytic conditions; however, it underwent degradation under acidic and alkaline environments. The major deterioration, Impurity components formed during the forced degradation investigation, have been isolated to identify and quantify compounds.  In alkaline conditions, three degradation products, designated as DP-1, DP-2, and DP-3, were formed, whereas acidic conditions yielded only one product (DP-4). A semi-preparative HPLC purification technique was used to isolate the identified degradation components. The compounds were characterised through high-resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR) analyses, which included ¹H NMR, ¹³C NMR, heteronuclear single quantum coherence (HSQC), and heteronuclear multiple bond correlation (HMBC) techniques.