Development of a RP-LC method for a diastereomeric drug valganciclovir hydrochloride by enhanced approach

Two methods, prescribed in USP, for the analysis of related substances of valganciclovir hydrochloride drug substance, were evaluated in terms of selectivity and ease of use. A new, simple, selective, stability indicating and user friendly RP-LC method was developed for related substances analysis. The developed single method is capable of separating all known impurities, which are quantified by two methods of USP. A central composite design was applied to optimize the critical chromatographic parameters. A multi step gradient program was strategically designed and a part of the program was optimized through Design of Experiments. Separation was achieved with a Zorbax SB C18 column with 0.1% trifluoro acetic acid and methanol in gradient elution. Design space is proposed graphically for the robust operation of the method. The method is linear, precise and accurate from LOQ level to 150% level of specification limit of impurities. Simple modification in the gradient program with reduced run time is also proposed for assay and diastereomer ratio. (C) 2012 Elsevier B.V. All rights reserved.