Abstract
Two stability-indicating methods were developed and validated for determination of valacyclovir HCl (VAC) in the presence of its degradation product, acyclovir. The first was a TLC-densitometric method, in which chloroform : methanol : ammonia (50 : 14 : 2 v/v/v) was used as a mobile phase. Silica gel 60 F-254 was used as a stationary phase and the chromatogram was scanned at 253 nm. Using this chromatographic system, VAC can be readily separated from its degradation product and gives a compact spot at an R-F value of (0.55 +/- 0.03). The peak area concentration plot is rectilinear over the range 20-300 ng per band. The second method represents the first attempt for spectrofluorimetric determination of VAC. The method was based on the reaction between VAC and 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) in an alkaline medium (pH 8.5) to form a highly fluorescent product that was measured at 500 nm after excitation at 465 nm. The fluorescence intensity concentration plot is rectilinear over the range 1-10 mu g ml(-1). The proposed methods were successfully applied for the determination of VAC in its commercial tablets with average percentage recovery of 100.13 +/- 0.33 and 98.50 +/- 1.75 for TLC-densitometric and spectrofluorimetric methods, respectively, without interference from common excipients. The results of the proposed methods were statistically analyzed and found to be in accordance with those given by a reported method. In addition the proposed methods were extended to a stability study of VAC, where the drug was exposed to acidic, alkaline, oxidative and photolytic degradation according to ICH guidelines.