QUANTITATIVE STRUCTURE-RETENTION RELATIONSHIPS OF ACYCLOVIR ESTERS USING IMMOBILIZED ALBUMIN HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY AND REVERSED-PHASE HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY

Acyclovir and 18 of its esters have been investigated by systematic measurement of their reversed-phase high-performance liquid chromatographic retention using differing mobile phase compositions. The methanol content of the mobile phase was varied between 5 and 95%. By linear least squares regression of the logarithmic retention factor (log k') against methanol concentration, the slope (S) and intercept (log k'(0)) of the so obtained straight lines were calculated for each compound. The chromatographic hydrophobicity index (phi(0,MeOH)) calculated from the S and log k'(0) values (phi(0,MeOH) = - log k'(0)/S) showed significant correlation (r > 0.96) to the calculated octanol-water partition coefficients (clog P). The albumin-binding properties of the compounds were characterised by the log k'(HSA) values obtained by using an immobilised human serum albumin (HSA) HPLC column and 1% propan-2-ol 99% aqueous 10 mM phosphate buffer pH 7.0 as mobile phase. The measured albumin-binding parameters showed significant correlations to the clog P,phi(0,MeOH), S and log k'(0) values, establishing the importance of hydrophobic properties to the interaction of the acyclovir derivatives with HSA.