Second derivative spectrophotometric determination of partition coefficients of phenothiazine derivatives between human erythrocyte ghost membranes and water

The absorption spectra of six phenothiazine derivatives, chlorpromazine, triflupromazine, promazine, promethazine, trifluoperazine and prochlorperazine, measured in the solutions containing various amounts of human erythrocyte ghosts (HEG) showed bathocromic shifts according to the amount of HEG. Due to the strong background signals caused by HEG, the baseline compensation was incomplete, even though the sample and the reference solutions contained the same amount of HEG, hence further spectral information could not be obtained. The second derivative spectra of these absorption spectra clearly showed the derivative isosbestic points, indicating that the residual background signal effects were entirely eliminated. The derivative intensity differences of the phenothiazines (Delta D values) before and after the addition of HEG were measured at a specific wavelength. Using the Delta D values, the partition coefficients (K-p) of these drugs were calculated and obtained with R.S.D. of below 10 %. The fractions of partitioned phenothiazines calculated from the K-p values agreed well with the experimental values. The results indicate that the derivative method can be applicable to the determination of partition coefficients of drugs to HEG without any separation procedures. (C) 1998 Elsevier Science B.V. All rights reserved.