Statistically Designed, Targeted Profile UPLC Method Development for Assay and Purity of Haloperidol in Haloperidol Drug Substance and Haloperidol 1 mg Tablets

Abstract

In view of the US pharmacopeia (USP)-proposed general chapter $$\left\langle {1220} \right\rangle$$ “The Analytical Procedure Lifecycle” and ICH-proposed ICHQ14 guideline “Analytical Procedure Development”, application of quality by design approach during analytical method development gains a significant importance. Methods developed by QbD approach will be more robust and thereby decrease efforts for method performance verification and post approval changes. Additionally, these methods will be more QC friendly as out of trend or out of specification results due to incompetent methods will be reduced and it will support the approach of life cycle management for analytical procedures. The present study deals with the development of an analytical targeted profile (ATP)-based, rapid, specific, precise, and mass-compatible RP-UPLC method with proven design space (DS) for the quantitative determination of Haloperidol and its degradation products in Haloperidol drug substance and Haloperidol 1 mg tablets. Using 5 different column chemistries, 4 different pH ranges, oven temperatures, and flow rates as variables experiments were carried out and statistically evaluated to finalize the chromatographic conditions. The significance and interaction effects of variables on the critical attributes (tailing factor and resolution) were evaluated through statistical analysis like analysis of variance (ANOVA). DOE study was also applied for the sample preparation to prove robustness of the sample preparation procedure. Forced degradation study was carried to demonstrate the stability-indicating nature of the method. Validation for active and available impurities was performed as per ICH and ANVISA guidelines and the method was found to be linear, accurate, specific, precise, and robust. Specificity of the method was confirmed orthogonally using QDa (mass detector) along with PDA detector. The method can be employed for release and stability testing of Haloperidol drug substance as well as Haloperidol 1 mg tablets.