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

Abstract

BACKGROUND\nRecent incorporated spectrophotometer software supporting mathematical methods was considered as an optimum key for the resolution of multicomponent mixtures.\n\n\nOBJECTIVE\nSeveral spectrophotometric techniques are introduced for the determination of mixtures of Tretinoin (TN), Hydroquinone (HQ), and Fluocinolone acetonide (FA), in 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.\n\n\nMETHODS\nConstant 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 which are: derivative ration zero-crossing point method, factorized derivative ratio method, and double divisor derivative ratio method.\n\n\nRESULTS\nThe work is conducted over a concentration range of 1-10, 4-38, and 4-35\u2009µg/mL, for TN, HQ, and FA, respectively. The results obtained are compared statistically to each other and to the official methods showing no significant difference.\n\n\nCONCLUSIONS\nThe proposed methods are successfully applied for the simultaneous determination of the three drugs in presence of MP in synthetic mixtures and in their combined dosage form Trimelasma® cream with very good accuracy and precision.\n\n\nHIGHLIGHTS\nComparative 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 mixture.