A new selective colorimetric method coupled with a high-resolution UV method for the consecutive quantification of three drugs in semi-solid preparations

Abstract

Triderm® cream and ointment contain clotrimazole (CLO), betamethasone dipropionate (BET), and the poor UV absorbing gentamycin (GEN), in addition to the preservative benzyl alcohol (BEN) which exists only in a cream preparation. A green, selective colorimetric approach was elaborated to increase the sensitivity of GEN quantification in Triderm® preparations, which depends on the immediate formation of a pink ion-pair between GEN and erythrosine (ERY) reagent in an aqueous acidic medium. The ion pair was made soluble in water with the assistance of the surfactant agent poloxamer 188 which is presented in this manuscript as an efficient solubilizing agent for the hydrophobic ion-pair. This surfactant agent has the feature of not affecting the native color of ERY, additionally the ease of preparing its aqueous solution with no need for heating or long waiting. The resulting complex GEN-ERY was measured directly at 545nm. This colorimetric approach was coupled with the Unlimited Derivative Ratio (UDD), which is a new smart UV method employed for the concurrent quantification of BET and CLO in Triderm® preparations without any intervention from BEN, due to its capability to resolve an extremely overlapped ternary spectrum that has no extended part, iso-absorptive point or robust zero crossing point. The newly developed UDD method depends on filtrating and measuring the signal of BET and CLO through calculating the equality factor(F) for CLO and BET after dividing their spectrum by BEN spectrum, derivatizing the resulting ratio spectrum, then constructing a regression equation employing the F factor for each BET and CLO. The overlapping excipient BEN was quantified via the Double Divisor Ratio spectra derivative method (DDR) relying on using a divisor comprising of a mix of BET + CLO. The advanced spectrophotometric approach validity was checked by confirming the linearity, accuracy, precision, and specificity in accordance with the ICH directions. NO notable difference when statistically comparing the newly established approach to the reference approach.