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

Absorption spectra of chlorpromazine and promazine in the presence of lecithin (egg yolk) bilayer vesicles were measured against the referen ce solutions containing the same amount of lecithin vesicles alone and their second derivative spectra were obtained by the Savitzky-Golay m ethod. 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 derivativ e intensity change (do) induced by the addition of the lecithin vesicl es was measured at the lambda(max) of each drug, and from the relation ship between the do value and the lipid concentration, the partition c oefficients (K(p)s) were calculated. The fractions of partitioned chlo rpromazine and promazine calculated by using the obtained K-p values a greed 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 lipi d vesicles, the proposed method can be applied to the determination of their partition coefficients without disturbing the equilibrium condi tions by separation procedures.