PREDICTION OF DRUG-BINDING TO MELANIN USING A MELANIN-BASED HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC STATIONARY-PHASE AND CHEMOMETRIC ANALYSIS OF THE CHROMATOGRAPHIC DATA

The high-performance liquid chromatographic retention parameters (k) h ave been determined for a series of 29 phenothiazines and related drug s. The k values were obtained on a hydrocarbon-bound silica stationary phase, an aminopropyl stationary phase and an aminopropyl phase coate d with melanin. Polycratic retention data determined on a hydrocarbona ceous column were extrapolated to 0% of organic modifier in binary aqu eous eluent yielding the chromatographic hydrophobicity parameter, log k(w)'. Logarithms of capacity factors determined isocratically on the aminopropyl column were subtracted from analogous values obtained wit h the same column loaded with melanin. The resulting parameter, log k( m-a)', in combination with log k(w)' produced a regression equation (c orrelation coefficient r = 0.953 1, significance level p = 10(-6)) whi ch could be used to describe drug-melanin binding efficiency, E(B). Th eoretical E(B) values were calculated by means of the derived equation for the whole series of 29 drugs chromatographed. The efficiency of b inding, E(B) to synthetic melanin was also determined by an ultrafiltr ation method for fifteen members of the series. No statistically signi ficant differences were observed between the E(B) values calculated us ing the chromatographic and ultrafiltration approaches. The results in dicate that chemometric analysis of the appropriate chromatographic da ta is a practical method for the evaluation of melanin binding.