Three Different Approaches Based on Derivative Ratio Spectra for Spectrophotometric Resolution of a Quaternary Mixture in Semisolid Dosage Form

Abstract

Abstract Background Recent incorporated spectrophotometer software supporting mathematical methods was considered as an optimum key for the resolution of multicomponent mixtures. Objective Several spectrophotometric techniques are introduced for the determination of mixtures of tretinoin (TN), hydroquinone (HQ), and fluocinolone acetonide (FA), in the presence of the preservative methyl paraben (MP), without any separation procedure, taking into consideration the presence of two minor components and the severe overlap of their spectra. Method Constant multiplication coupled spectrum subtraction resolved the quaternary mixture into the zero-order absorption spectrum of TN alone and a severely overlapped, ternary mixture of HQ, FA, and MP. Three approaches based on the derivative ratio spectra were applied to resolve this ternary, severely overlapped mixture: derivative ratio-zero-crossing point method, factorized derivative ratio method, and double divisor derivative ratio method. Results The work was conducted over a concentration range of 1–10, 4–38, and 4–35 µg/mL, for TN, HQ, and FA, respectively. The results obtained were compared statistically to each other and to the official methods, showing no significant difference. Conclusions The proposed methods were successfully applied for the simultaneous determination of the three drugs in the presence of MP in synthetic mixtures and in their combined dosage form (Trimelasma® cream) with very good accuracy and precision. Highlights This was a comparative study between conventional and new methods for resolving ternary, severely overlapped mixtures. Mathematical manipulation steps and enrichment techniques aided accurate quantification of the minor components in mixtures.