Determination of Dapiprazole Hydrochloride in the Presence of Process and Degradation Impurities by a Validated Stability Indicating RP-HPLC Method

Abstract

Dapiprazole hydrochloride is an α-adrenergic blocking agent 1,2. Chemically, it is 5,6,7,8-tetrahydro-3-[2-(4-o-tolyl-1-piperazinyl)ethyl]-s-triazolo[4,3-a] pyridine hydrochloride 3 (empirical formula C19H27N5•HCl, m.w. 361.93). It is a sterile, white, lyophilized powder soluble in water. Dapiprazole hydrochloride ophthalmic solution is indicated in the treatment of iatrogenically induced mydriasis produced by adrenergic (phenylephrine) or parasympatholytic (tropicamide) agents 4. The aim of this paper was to develop validate a simple and reliable HPLC-UV method for the simultaneous determination of dapiprazole and its process related impurity-A. Besides the simple route of synthesis for dapiprazole, we have observed a potential impurity (Imp-A) in our synthetic process and some unknown impurities in forced degradation. Hence, a stabilityindicating HPLC method for determination of dapiprazole in presence of process and degradation impurities was developed and validated as per International Conference on Harmonization (ICH) guidelines. This manuscript describes the development and validation, in accordance with ICH guidelines, of a rapid, economical, precise and accurate stability-indicating isocratic reversed-phase HPLC method for analysis of dapiprazole in the presence of its process related impurity. This paper also deals with the forced degradation of dapiprazole under the stress conditions acidic and basic hydrolysis, oxidation, heat and light and validation of the method for accurate quantification