Stability indicating HPLC method development and validation for the determination of organic impurities of cariprazine hydrochloride, their characterization by LC-MS and NMR techniques.

Cariprazine hydrochloride is an antipsychotic drug used to treat diseases such as schizophrenia and acute mania in adults. Quality determination of the cariprazine drug molecule is a critical aspect to ensure maximum drug efficacy and to minimize side effects caused by unwanted substances commonly referred to as impurities, formed during manufacturing. Hence, this study aims to develop a chromatographic method for the determination of organic impurities present in cariprazine hydrochloride. A stability-indicating and robust method was developed using reverse-phase high-performance liquid chromatography (HPLC). The analytical method involves the simple preparation of a mobile phase consisting of 0.2% orthophosphoric acid in HPLC grade water as mobile phase A, and acetonitrile as mobile phase B. Separation was achieved using a YMC Pack Pro C18 column (150 mm × 4.6 mm, 3 μm), with a step gradient at a flow rate of 1.0 mL/min and detection at λmax 215 nm for the quantitation of organic impurities. The method is capable of detecting impurities at the 0.01% level and quantifying them at the 0.03% level with respect to the test concentration. It was found to be linear, accurate, and precise over the range from the LOQ to 200% of the specification limit of impurities. The method was specific to all degradation products formed during forced degradation studies, thereby demonstrating its stability-indicating nature. The mass balance was found to be within the tolerance limit of 95-105%. All impurities, including process-related and degradation products, were characterized using mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy. The spectroscopic data confirmed the structures of the impurities. Overall, the method is useful for determining the quality of cariprazine hydrochloride in quality control.