NOVEL SPECTROPHOTOMETRIC METHODS UTILIZING NORMALIZED SPECTRUM FOR SIMULTANEOUS DETERMINATION OF KETOCONAZOLE AND CHLORHEXIDINE IN THEIR BINARY MIXTURE
Normalized spectra manipulating spectrophotometric methods were proposed for simultaneous determination of ketoconazole (KET) and chlorhexidine acetate (CHD) in their binary mixture. The proposed methods were simultaneous ratio difference (SRD), simultaneous derivative ratio (S1DD), and ratio H-point standard additions (RHPSAM).Main advantage of the first two methods was minimum manipulation procedure compared to conventional ratio difference or derivative ratio method, such that total concentrations of both drugs were determined directly at the isoabsorptive point in the ratio spectra. Subsequent difference or derivatization procedures were followed for SRD orS1DD, respectively. Concentration of KET was determined using either difference between peak amplitudes at 220 nm and 235 nm in SRD or peak to peak measured at 228 nm and 289 nm in S1DD. Then CHD concentration was simply determined by subtraction. In RHPSAM, calibration plots of the peak amplitudes to the corresponding added concentrations of KET at 220 nm and 232 nm were performed. Intersection of the two calibration lines "RH-point" was used to determine concentrations of both drugs. Where X and Y coordinates of RH-point were corresponding to KET and CHD concentrations, respectively. Linear regressions were obtained over the concentration ranges of 5.0-40.0µgmL-1 and 2.0-20.0 µgmL-1 for KET and CHD, respectively. Acceptable limits of accuracy, precision and specificity were obtained for the proposed methods, along with accurate determination of pharmaceutical formulation. Finally, statistical analysis between the proposed methods and reported RP-HPLC one showed no significant difference