DETERMINATION OF 2'-BETA-FLUORO-2',3'-DIDEOXYADENOSINE, AN EXPERIMENTAL ANTI-AIDS DRUG, IN HUMAN PLASMA BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY

2'-beta-Fluoro-2',3'-dideoxyadenosine (F-ddA, lodenosine) is an experi mental anti-AIDS drug currently being evaluated in a Phase I clinical trial. A simple and specific HPLC method with UV detection, suitable f or use in clinical studies, has been developed to determine both F-ddA and its deaminated catabolite, 2'-beta-fluoro-2',3'-dideoxyinosine (F -ddI) in human plasma. After inactivation of plasma HIV by 0.5% Triton X-100, the compounds of interest are isolated and concentrated using solid-phase extraction. Processed samples are separated by use of a pH 4.8 buffered methanol gradient on a reversed-phase phenyl column. The method has a linear range of 0.05-5 mu g/ml (0.2-20 mu M) and intra-a ssay precision is better than 8%, Analyte recovery is quantitative and plasma protein binding is minimal. In addition, drug and metabolite l evels measured in Triton-treated human plasma remain stable for at lea st 5 months when samples are stored frozen without further treatment. Compound concentrations determined after samples are processed and the n frozen for up to 1 month before analysis are also unchanged. Publish ed by Elsevier Science BN.