HPLC METHOD DEVELOPMENT AND VALIDATION FOR ANTI-PSYCHOTIC DRUGS: A REVIEW

Gali Haritha*, Sara Jabeen, Arunabha Mallik

ABSTRACT

Anti-psychotic drugs (APDs) remain the cornerstone of therapy for schizophrenia, bipolar disorder, psychosis associated with depression, and several behavioral conditions. With expanding therapeutic use and the emergence of newer atypical antipsychotics, the need for reliable, accurate, and stability-indicating analytical methods has increased significantly. High-Performance Liquid Chromatography (HPLC) continues to be the most widely used technique for quantification of APDs in bulk, formulations, and biological matrices due to its sensitivity, robustness, and applicability to a broad range of physicochemical characteristics. This review summarizes the principles of HPLC method development for APDs, including selection of stationary phase, mobile phase optimization, buffer selection, pH adjustment, detection wavelength, flow rates, and system suitability parameters. Comprehensive literature covering typical and atypical antipsychotics such as haloperidol, risperidone, olanzapine, clozapine, quetiapine, aripiprazole, ziprasidone, Amisulpride, and Lurasidone is discussed. Detailed validation parameters in accordance with ICH Q2 (R1) are provided, including accuracy, precision, linearity, robustness, ruggedness, LOD, LOQ, specificity, and forced-degradation behavior. Challenges in the analysis of multi-component APD combinations, metabolite interference, and green analytical practices are highlighted. Future directions emphasize AQbD-based method development, UHPLC, greener solvents, and advanced detection technologies. This review aims to support researchers and analytical scientists in designing efficient HPLC methods for modern antipsychotic pharmaceuticals.

Keywords: HPLC, Anti-Psychotic Drugs, Typical and Atypical Antipsychotics, Method Development, Validation, ICH Q2 (R1), Stability-Indicating Methods, AQbD, UHPLC.