Stability-Indicating Validated Novel RP-HPLC Method for Simultaneous Estimation of Methylparaben, Ketoconazole, and Mometasone Furoate in Topical Pharmaceutical Dosage Formulation

A simple, specific, precise, and accurate RP-HPLC method has been developed and validated for simultaneous estimation of Methylparaben (MP), Ketoconazole (KT), and Mometasone Furoate (MF) topical pharmaceutical dosage formulation. The separation was achieved by Waters X Terra C18 column using mobile phase consisting of buffer (triethyl amine in water, pH adjusted to 6.5 with glacial acetic acid)-acetonitrile (40？:？60,？v/v) at a flow rate of 1.5？mL/min and detection at 250？nm. The method showed linearity with correlation coefficient <0.9999 over the range of 0.12–15.2？μg/mL, 0.67–149.4？μg/mL, and 0.42–7.6？μg/mL for MP, KT, and MF, respectively. The mean recoveries were found to be in the range of 99.9–101.1% for all the components. The method was validated as per the ICH guidelines for linearity, limit of detection, limit of quantification, accuracy, precision, robustness and solution stability. Stability indicating capability of the developed method was established by analyzing forced degradation of samples in which spectral purity of MP, KT, and MF along with separation of degradation products from analytes peak was achieved. The method can be successfully applied for routine analysis of quantitative determination of MP, KT, and MF in pharmaceutical dosage form. 1. Introduction Mometasone Furoate (MF), (11β, 16α)-9, 21-dichloro-11-hydroxy-16-methyl-3, 20-dioxopregna-1, 4-dien-17-yl 2-furoate (Figure 1(a)) is a topical corticosteroid; it has anti-inflammatory, antipruritic, and vasoonstrictive properties. Mometasone inhibits the action of allergic reactions, eczema, and psoriasis that cause inflammation, redness, and swelling [1, 2]. Ketoconazole (KT), an imidazole derivative, chemically 1-[4-(4-{[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]ethan-1-one (Figure 1(b)) is an antifungal agent with topical and systemic action and can be incorporated into several pharmaceutical forms. As for example a ketoconazole shampoo is effective against seborrhoeic dermatitis as well as Pityriasis versicolor [3–7]. KT and MF in combined dosage form are used in the treatment of mild to moderate inflamed cutaneous mycoses with antimycotic activity. Figure 1: Chemical structure of (a) Mometasone Furoate, (b) Ketoconazole, and (c) Methylparaben. The preservative system is an important part of semisolid formulations in preventing the deterioration of formulations from microbial contamination. Methylparaben (MP) (Figure 1(c)) and its salts are most commonly used as preservatives for many years. To establish their