2ND-DERIVATIVE SPECTROPHOTOMETRIC DETERMINATION OF PARTITION-COEFFICIENTS OF CHLORPROMAZINE AND PROMAZINE BETWEEN LECITHIN BILAYER VESICLES AND WATER

Absorption spectra of chlorpromazine and promazine in the presence of lecithin (egg yolk) bilayer vesicles were measured against the reference solutions containing the same amount of lecithin vesicles alone and their second derivative spectra were obtained by the Savitzky-Golay method. The residual background signal effects by the lecithin vesicles observed in the absorption spectra were entirely eliminated and both drugs clearly showed three derivative isosbestic points. The derivative intensity change (do) induced by the addition of the lecithin vesicles was measured at the lambda(max) of each drug, and from the relationship between the do value and the lipid concentration, the partition coefficients (K(p)s) were calculated. The fractions of partitioned chlorpromazine and promazine calculated by using the obtained K-p values agreed well with the experimental values. For the drugs which have the nature of metachromasy between the lipid vesicles and water, and even whose absorption bands overlap with the background signals by the lipid vesicles, the proposed method can be applied to the determination of their partition coefficients without disturbing the equilibrium conditions by separation procedures.