DETERMINATION OF SELF-ASSOCIATION OF IRINOTECAN HYDROCHLORIDE (CPT-11) IN AQUEOUS-SOLUTION

Self-association of irinotecan hydrochloride (CTP-11) in an aqueous solution was studied using UV, circular dichroism (CD), H-1-NMR and the quasi-elastic light scattering (QLS) method. The UV spectra showed a hypochromic effect in the aqueous solution. In the CD spectra, typically positive Davydov splitting was observed and the DELTAepsilon value was reduced sigmoidally when the concentration of CTP-11 was decreased. In the H-1-NMR, the aromatic signals of higher concentration shifted to a diamagnetic direction compared with those of lower concentration. These observations suggested that CPT-11 molecules are present as monomer in the lower concentration, and the self-association with positive helicity occurs by vertical stacking more than 10 muM of concentration. Its molecules form complete aggregates at more than 2 mm of the concentration. Results of QLS which coincided in the prediction of partition coefficient experiments suggested that CPT-11 molecules formed dimer under the condition. By the regression analysis of CD spectral data, the equilibrium constant for the self-association was calculated to be 2.41 x 10(-4) M-1.