Abstract
A simple reversed phase high-performance liquid chromatographic method was established for the separation and quantification of a novel prodrug of zidovudine in rat plasma. Zidovudine was one of the original drugs used to treat HIV infection. Appropriate aliquots of rat plasma were spiked with cholesteryl carbonate zidovudine (AZTC) and treated with acetonitrile to precipitate plasma proteins. The supernatant after supercentrifugation was collected and an aliquot of 20μL was injected directly into an HPLC system consisting of a Diamonsil™ C18 column and a diode array detector. The mobile phase consisted of methanol (85%, v/v) and diethyl ether (15%, v/v) at a flow rate of 1.0mL/min. The extraction recoveries of AZTC at the three concentrations examined were all higher than 80%. The HPLC assay was linear over the concentration range 0.5–80μg/mL. A one-compartment model with apparent first-order elimination was used to describe the plasma concentration–time profile for AZTC after administration via the tail vein. The mean elimination half-life (t1/2) was 292.4min. This RP-HPLC method will be useful for the evaluation of the pharmacokinetics of AZTC in rats.
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