Development and Validation of a Novel and Cost‐Effective RP‐HPLC Method for the Separation of an Isomeric Impurity in Cariprazine Hydrochloride, an Antipsychotic Agent

Cariprazine is an active pharmaceutical ingredient; it is indicated for the treatment of schizophrenia and depressive episodes associated with bipolar disorder. It is also employed in the management of treatment of major depressive disorder. A specific, novel, and reverse-phase high-performance liquid chromatography (RP-HPLC) method was developed for the analysis of cis isomer (isomeric impurity) in cariprazine hydrochloride, and this method is validated as per ICH guideline. By reviewing online sources, it was noted that no literature is available related to the separation of cis isomer from the cariprazine hydrochloride drug molecule. RP-HPLC method was developed using stationary phase as Intersil C8, 250 mm, 4.6 mm, 5 μm. Gradient elution was employed using mobile phase A, which consisted of a 0.05 M monobasic ammonium phosphate (NH₄H₂PO₄) buffer adjusted to pH 6.0 ± 0.05 with triethylamine; mobile phase B consisted of a homogeneous combination of acetonitrile and water (80:20, v/v). The chromatographic separation was performed at a flow rate of 1.2 mL/min, with the column oven temperature maintained at 35°C and the detection wavelength set at 215 nm. The total run time of this method is 20 min. The selected diluent was a mixture of acetonitrile, water, and 88% orthophosphoric acid in a volumetric ratio of 60:40 and 0.1 v/v/v. The developed method is robust, precise, accurate and linear in a series of LOQ to 500% level from the specification concentration limit. The newly developed RP-HPLC method is applicable for the analysis of cis isomer in cariprazine hydrochloride samples.