THE EFFECT OF OCTANOIC-ACID ON THE BINDING OF THE ENANTIOMERS OF IBUPROFEN AND NAPROXEN TO HUMAN SERUM-ALBUMIN - A CHROMATOGRAPHIC IMPLICATION

Purpose. The heats of reaction between the enantiomers and racemates o f ibuprofen and naproxen and human serum albumin (HSA) are to be measu red with and without the addition of octanoic acid. The effects of oct anoic acid on the free energies of interaction between the drugs and H SA is to be determined and compared to that estimated from theoretical equations. Methods. The heats of reaction have been measured directly by flow microcalorimetry. Results. The data showed that octanoic acid lowered the 1:1 binding constants for all the drug-HSA interactions i nvestigated. The effect of octanoic acid was greater on the R than on the S forms of the drugs as shown by the differences in free energies of interaction in the presence and absence of octanoic acid. Conclusio ns. The increased free energy differences for the binding of the enant iomers of both drugs to HSA in the presence of octanoic acid is closer to the value deemed to be necessary for the separation of enantiomers by Davenkov, and shows the importance of the addition of octanoic aci d to the mobile phase in the separation of these enantiomers on immobi lized albumin columns.