Abstract

A sensitive, precise and environmentally friendly stability indicating Rapid Resolution Liquid Chromatographic (RRLC) method for the determination of valaciclovir HCl in presence of its degradation products was developed and validated. An isocratic separation was achieved using Zorbax SB phenyl column with flow rate of 0.3 mL min^-1 and UV detection at 254 nm. The mobile phase was a mixture of 0.01M n-tetrabutyl ammonium hydrogen sulfate (pH 2.5, adjusted using 0.1M NaOH) and methanol in the ratio of (95:5, v/v). The stability of valaciclovir HCl has been studied under different stress conditions. The acid-and alkaline-hydrolysis products were identified and were suggested to be guanine and aciclovir, respectively. Complete separation of valaciclovir hydrochloride and its degradation products was achieved in overall run time of approximately 6.0 min with low mobile phase consumption and waste production (1.8ml/run). The method was linear over the range of 0.4 µg mL^-1 to 40.0 µg mL^-1 (r=0.9999) with limit of detection and quantitation of 0.10 µg mL^-1 and 0.36 µg mL^-1, respectively. The high efficiency and unique selectivity of developed method enabled its adoption for determination of aciclovir, the active metabolite of valaciclovir, in spiked human plasma.

Keywords: Liquid chromatography, stability indicating, plasma, valaciclovir and aciclovir.