Development of official assay method for loperamide hydrochloride capsules by HPLC

Currently, the potentiometric titration and the high pressure liquid chromatography (HPLC) method were utilized in Korean Pharmacopoeia XII (KP XII) as well as other pharmacopoeias (USP, EP, BP) for determination of loperamide hydrochloride in raw materials and capsules, respectively. The research objective is to overcome the remaining drawbacks from current methods such as solubility of mobile phase (KP XII), less scientific approach (USP 43) or using paired-ion chromatography reagent which shows some limitations (BP2017 and other formulation monographs). The proposed method was optimized by Design of Experiment (DoE) tool to obtain the satisfied method for determination of loperamide hydrochloride. The optimal condition was performed on the common C18 column (150 mm × 4.6 mm; 5 ㎛) using isocratic elution with the mobile phase containing 40 mM of potassium phosphate monobasic (pH 3.0) and acetonitrile (56:44), at a flow rate of 0.7 mL/min. The optimized method was validated and met the requirements of the International Conference on Harmonization. The developed method was applied to determine loperamide hydrochloride in capsules and can be used to update the current monograph in KP XII.