Successive ratio subtraction coupled with constant multiplication spectrophotometric method for determination of hydroquinone in complex mixture with its degradation products, tretinoin and methyl paraben

• Successive ratio subtraction–constant multiplication spectrophotometric method was developed.
• Resolving hydroquinone, tretinoin, hydroquinone polymer, 1,4 benzoquinone, and methyl paraben
• Avoid using hydroquinone formulation at mild alkali condition
• Hydroquinone was polymerized in an alkali medium.
• Toxic 1,4 benzoquinone formed when pharmaceutical formulation subjected to mild alkali condition.

A sensitive and selective stability-indicating successive ratio subtraction coupled with constant multiplication (SRS-CM) spectrophotometric method was studied and developed for the spectrum resolution of five component mixture without prior separation. The components were hydroquinone in combination with tretinoin, the polymer formed from hydroquinone alkali degradation, 1,4 benzoquinone and the preservative methyl paraben. The proposed method was used for their determination in their pure form and in pharmaceutical formulation. The zero order absorption spectra of hydroquinone, tretinoin, 1,4 benzoquinone and methyl paraben were determined at 293, 357.5, 245 and 255.2 nm, respectively. The calibration curves were linear over the concentration ranges of 4.00–46.00, 1.00–7.00, 0.60–5.20, and 1.00–7.00 μg mL− 1 for hydroquinone, tretinoin, 1,4 benzoquinone and methyl paraben, respectively. The pharmaceutical formulation was subjected to mild alkali condition and measured by this method resulting in the polymerization of hydroquinone and the formation of toxic 1,4 benzoquinone. The proposed method was validated according to ICH guidelines. The results obtained were statistically analyzed and compared with those obtained by applying the reported method.

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