The effect of a functional group in penicillin derivatives on the interaction with bile salt micelles studied by micellar electrokinetic chromatography

A capillary electrophoresis method is developed and validated for the chara cterization of the affinity and the interaction between aminopenicillanic a cid (APS-H) and its derivatives with bile salt micelles. The micellar syste ms studied contained sodium taurocholate (NaTC) and sodium deoxycholate (Na DC). Using the retention factor k ', functional group selectivity, Gamma (G ), is defined as the ratio of the retention factor of a substituted aminope nicillanic acid (APS-R) over the capacity factor of APS-H and the differenc e in free energy (Delta DeltaG degrees) can be used for the characterizatio n of the affinity and interaction between drugs and micelles. The functiona l group selectivity is a direct measure of the interaction of the functiona l group with micelles. The calculated Delta DeltaG degrees value gives info rmation on the partition equilibrium and interaction between drugs and mice lles. A positive Delta DeltaG degrees value means that the interaction of a functional group Gamma (G) to the APS-H leads to a decrease in the interac tion with the micelles. A negative Delta DeltaG degrees value, on the other hand, has the opposite meaning. The results obtained in this study exhibit ed that these APS-R compounds have smaller affinity to the micelles compare d to unsubstituted APS-H. Furthermore, the log k ' of the drugs in these sy stems were correlated with the log P-OW in the n-octanol/water system and w ith log P-G (permeation coefficient).