A comprehensive forced degradation studies of Cariprazine hydrochloride using LC-HRMS/MS and in silico toxicity predictions of its degradation products

Abstract

Cariprazine hydrochloride is a second-generation antipsychotic drug and has been approved by the US Food and Drug Administration and the European Medicines Agency. Herein, we have reported a stability-indicating assay method for the Cariprazine hydrochloride and characterization of its major degradation products using LC-HRMS/MS. The drug substance Cariprazine hydrochloride was subjected to acid, base, oxidation, thermal and photolytic stress degradation. A total of five novel degradation products (DP-1 to DP-5) of Cariprazine hydrochloride drug substance were formed under various acid, base and oxidative conditions. In silico toxicity of the degradation products was evaluated using Leadscope prediction platform. We successfully separated Cariprazine Hydrochloride peak from degradation products (DP-1 to DP-5) by using gradient elution on an Inertsil C18 column (150 × 4.6 mm, 5 µm). The drug substance was found to be labile to acidic, alkaline hydrolytic, and oxidative conditions and stable to photolytic and thermal stress conditions. The degradation pathways were delineated by explaining the putative mechanism of degradation in various conditions. The stability-indicating assay method was validated according to the ICH guideline and hence can be used for routine quality control and stability study analysis of Cariprazine hydrochloride in pharmaceutical industries and research laboratories.