Development and Validation of a Reverse-phase HPLC Method for the Assay of Hydrocodone Bitartrate, Chlorpheniramine Maleate, Methylparaben and Propylparaben in Extended-release Oral Suspension

摘要

Hydrocodone Bitartrate and Chlorpheniramine Maleate Oral Solution, is a commonly available drug product used to relieve cough and symptoms associated with upper respiratory allergies or the common cold. It consists of two main Active Pharmaceutical Ingredients (API's), Hydrocodone Bitartrate and Chlorpheniramine Maleate. It also contains Methylparaben and Propylparaben which, serve as preservatives and provide anti-fungal capabilities. The purpose of this project was to develop an efficient reverse-phase assay method using HPLC that is stability indicating, robust, rugged, precise, linear, accurate and capable of being replicated in different laboratories. In order for a method to be considered effective and be utilized to test and release products, it must be validated according to the ICH Guideline Q2(R1). The validation parameters evaluated were: system suitability, specificity, forced degradation, linearity, accuracy/recovery, precision, ruggedness/intermediate precision, filter study, solution stability and robustness. The method was developed and validated for a concentration range of 60-180 ppm for Hydrocodone Bitartrate, 48-144 ppm for Chlorpheniramine Maleate, 45-135 ppm for Methylparaben and 9-27 ppm for Propylparaben (50% to 150% of the specification). Specificity of the method was also established and forced degradation was performed. The method was found to be specific, stability indicating, precise, accurate and robust. However, during the robustness portion of the validation, the method was found to be sensitive to the reduction of organic solvent in mobile phase A composition. In addition, working standards and sample solutions were deemed stable up to 4 days, while the stock standard solutions are stable up to 33 days when stored at room temperature.