Reversed phase HPLC determination of zidovudine in rat plasma and its pharmacokinetics after a single intranasal dose administration.

Abstract

The development and validation of a simple and accurate method based on HPLC with ultraviolet detection for the quantification of zidovudine in rat plasma and its application to a pharmacokinetic study following a single intranasal dose zidovudine is described. Zidovudine was extracted from the plasma using a single-step deproteinization. Chromatographic separation of zidovudine from interfering components was achieved with a C-18 reverse phase column, a mobile phase consisting of a mixture of sodium acetate buffer (55 mM) with pH adjusted to 7.0 and acetonitrile (91:9 v/v) and UV detection set at 265 nm. The method was linear from 100 to 10,000 ng.mL(-1) (r(2) > or = 0.9995), and zidovudine had a mean recovery from plasma of 92.8%. The coefficient of variation of inter-day and intra-day quality control samples was less than 15%. After a single intranasal dose of zidovudine administered to rats, pharmacokinetic parameters (AUC(0-24), C(max), t(max), t(1/2)) were determined. The proposed method was found to be simple, specific, accurate, and precise and could be applied to the quantitative analysis of clinical pharmacokinetic studies of zidovudine in rats.