A NOVEL STABILITY-INDICATING UHPLC–MS/MS METHOD FOR QUANTITATIVE DETERMINATION OF BREXPIPRAZOLE IN BULK DRUG SUBSTANCE: DEVELOPMENT, VALIDATION, AND FORCED DEGRADATION STUDIES

Abstract

Background: Brexpiprazole is an atypical antipsychotic drug used to treat schizophrenia and agitation induced by Alzheimer's disease. Aim: The present study aimed to develop and validate a simple, rapid, sensitive, and stability-indicating UHPLC MS/MS method for measuring Brexpiprazole by using a dilute-and-shoot sample preparation technique. Method: Chromatographic separation was performed on a Shim-pack GIST C18 column using a mobile phase at 0.1% formic acid in water and acetonitrile. Electrospray ionization was performed in multiple reaction monitoring mode to detect the transition m/z 434.15 → 273.10. Result: The method showed excellent linearity between 1-100 ng/mL, with a correlation coefficient (r²) of 0.9976. Brexpiprazole has a retention period of 2.18 minutes, that allowed for rapid analysis. The limits of detection and quantification were found to be 0.45 and 1.0 ng/mL, respectively. Accuracy studies showed recoveries ranging from 89.0% to 96.8%, while precision tests achieved acceptable %RSD values. The Stability tests found that Brexpiprazole was stable under the investigated conditions, with no significant degradation. Conclusion: The novel UHPLC-MS/MS technique is rapid, sensitive, and reliable, excellent for routine pharmaceutical analysis, bioanalytical investigation, stability assessments, and pharmacokinetic applications.