Quality by design with design of experiments approach for the development of a stability‐indicating LC method for benzonatate and its impurities in liquid oral dosage form

Abstract

AbstractA quality by design based simple and stability‐indicating liquid chromatography method has been developed successfully for benzonatate and its related impurities. The optimized high‐performance liquid chromatography method can be used to detect and quantify the benzonatate impurities in its finished liquid oral dosage forms. For the quantification of impurities demands more comprehensive way of analytical method development. Quality by design approach allows the assessment of various analytical parameters and their effects with minimum number of experiments. The current method has been separated five specified known impurities of benzonatate along with unspecified degradation products with adequate chromatographic resolution. The separation was acquired by using Zorbax SB CN, (4.6 × 250 mm), 5 μm column at a flow rate of 0.9 mL/min with a gradient elution mode. Mobile phase A consisting of 15 mM monobasic potassium phosphate (pH of 2.7) and tetrahydrofuran (90:10 v/v) and mobile phase B was mixture of acetonitrile and tetrahydrofuran (90:10 v/v). Detection of compounds was carried out at 310 nm and column temperature was maintained at 35°C. The drug product and drug substance were subjected to the stress conditions such as acid, base, oxidation, heat, and photolysis as per the recommendations of International Conference on Harmonization (Q2) methodology. The method was validated to be precise, specific, robust, rugged, and stability indicating.