CHROMATOGRAPHIC STUDY ON THE SELF-ASSOCIATION OF CHLORPROMAZINE HYDROCHLORIDE IN SODIUM-CHLORIDE SOLUTION

The self-association of chlorpromazine hydrochloride (CPZ) in 154 mmol dm-3 sodium chloride solution is investigated by gel filtration chromatography (GFC) and spectrophotometry at 25-degrees-C. From the analysis of the centroid volume of the GFC elution pattern, the concentration C1 of CPZ monomer is determined as a function of total CPZ concentration C. From the concentration dependence of C1, the weight-average aggregation number n(w) of CPZ micelles is evaluated as a function of C. These results are quantitatively explained on the basis of formation of dimer and 38-mer. The dimerization constant thus obtained is close to that determined by spectrophotometry. At concentrations much lower than the cmc, the derivative GFC pattern for the leading boundary is sharper than that for the trailing boundary. Above the cmc, two maxima appear in the derivative pattern for the trailing boundary. These derivative patterns are well simulated on the basis of the above aggregation model and plate theory for GFC. A discrepancy in the literature cmc values is explained on the basis of the present results. Since CPZ dimerizes at physiologically active concentrations, this effect must be taken into consideration for the analysis of biological activities of CPZ.