Determination of pKa values of some butyrophenones, their sensitive LC-UV analysis in pharmaceutical dosage forms and stress degradation behavior under ICH-recommended stress conditions

In this study, pKa values of some ionizable butyrophenones, namely, benperidol, droperidol, and haloperidol were determined using by the dependence of the retention factor on pH of the mobile phase. The effect of the mobile phase composition on the ionization constant was studied by measuring the pKa at different methanol-water mixtures, ranging between 50 and 65% (v/v) using an LC-UV method. Additionally, a simple, accurate, precise, and fully validated analytical method for the simultaneous and individual determination of benperidol, droperidol, and haloperidol in their dosage forms was developed. Butyrophenones were exposed to thermal, photolytic, hydrolytic, and oxidative stress conditions, and the stressed samples were detected by the proposed method. © 2013 Copyright Taylor and Francis Group, LLC.