Analytical method development and validation of zuclopenthixol by RP-hplc in compliance with ichq2r1 guidelines

Abstract

Zuclopenthixol, a thioxanthene-class antipsychotic, is extensively used in the management of schizophrenia, bipolar disorder, and behavioural disturbances in patients with intellectual disabilities. Its therapeutic effect arises from potent antagonism at dopamine D1 and D2 receptors, producing marked sedative and antipsychotic activity. The present research focuses on developing and validating a simple, precise, and stability-indicating reversed-phase high-performance liquid chromatographic (RP-HPLC) method for the quantitative estimation of Zuclopenthixol in pharmaceutical formulations, following ICH Q2(R1) guidelines. Chromatographic separation was achieved using a Waters X-Bridge C18 (150 × 4.6 mm, 3.5 µm) column with a mobile phase of 20 mM potassium dihydrogen phosphate containing 0.1% v/v triethylamine and acetonitrile in a 45:55 v/v ratio at a flow rate of 1.0 mL/min. Detection was performed at 257 nm, and the drug showed a retention time of 5.52 minutes. The method exhibited excellent linearity (r² = 0.9945) over the concentration range of  25–150%, with mean recovery values between 98–102% and %RSD below 2%. Specificity was confirmed through forced degradation studies, demonstrating no interference from excipients or degradation products. The method was found robust and rugged under varied chromatographic conditions, ensuring reproducibility and reliability. Thus, the validated RP-HPLC method is accurate, precise, and suitable for routine quality control, assay determination, and stability evaluation of Zuclopenthixol in parenteral and other pharmaceutical dosage forms.