UHPLC assay and impurity methods for diphenhydramine and phenylephrine hydrochloride oral solution.

Many over-the-counter drug products lack official compendial analytical methods. As a result, the United States Pharmacopeia and the United States Food and Drug Administration are seeking to develop and validate new methods to establish analysis standards for the assessment of the pharmaceutical quality of over-the-counter drug products. Diphenhydramine and phenylephrine hydrochloride oral solution, a combination drug product, was identified as needing a compendial standard. Therefore, an ultra-high-performance liquid chromatography method was developed to separate and quantify the two drug compounds and eleven related organic impurities. As part of a robustness study, the separation was demonstrated using different high-performance liquid chromatography systems and columns from different manufacturers, and showed little dependence with changes in flow rate, column temperature, detection wavelength, injection volume and mobile phase gradient. The method was then validated conformant with the International Council for Harmonisation guidelines. For impurities, adequate specificity, linearity, accuracy and precision were demonstrated. For assay, a slight modification to the injection volume was necessary to achieve adequate analytical performance. With successful development and validation, these methods were shown to be suitable for their intended purpose and may be considered for adoption as compendial procedures.