Simultaneous Determination of Paracetamol and Diphenhydramine Hydrochloride in Presence of Paracetamol Degradation Product

Abstract

Three sensitive , selective and precise stability indicating methods for simultaneous determination of Paracetamol and Diphenhydramine hydrochloride in their binary mixture and in presence of P-aminophenol; the potential impurity and degradation product of Paracetamol; were developed. In Method A, Paracetamol was determined in presence of Diphenhydramine Hydrochloride and P-aminophenol using the first derivative ( 1 D) spectrophotometric method by measuring the peak amplitude at 264.5 nm where linear relationship was obtained in the range of 2-12 μg mL -1 while Diphenhydramine Hydrochloride was determined in presence of Paracetamol and P-aminophenol using the first derivative of ratio spectra ( 1 DD) method at 224 nm. Method B utilized chemometric techniques [Principal Component Regression (PCR) and Partial Least Squares(PLS)] which successfully applied to quantify both drugs and degradation product using the information included in the absorption spectra of appropriate solutions of the three compounds in the range of 220-340nm. Method C used HPTLC-densitometric method in which the aforementioned components were separated on silica gel plates using chloroform-ethyl acetate-ammonia solution (4:6:0.2, by volume) as a developing system. This was followed by quantitative densitometric measurement at 220 nm .Linear relationship were obtained in the concentration ranges of 0.4-1.6 μg/band , 3-12 μg /band and 0.4-1.6 μg/band for Paracetamol, Diphenhydramine Hydrochloride and P-aminophenol respectively. The proposed methods have been successfully applied to the analysis of Paracetamol and Diphenhydramine Hydrochloride in their pharmaceutical formulation without interference from other dosage form additives and the results were statistically compared with official method .