Development and validation of an UPLC method for rapid determination of ibuprofen and diphenhydramine citrate in the presence of impurities in combined dosage form.

ABSTRACT

A novel, stability-indicating gradient reverse-phase ultra-performance liquid chromatographic method was developed for the simultaneous determination of ibuprofen and diphenhydramine citrate in the presence of degradation products and process related impurities in combined dosage form. The method was developed using C18 column with mobile phase containing a gradient mixture of solvent A and B. The eluted compounds were monitored at 220 nm. Ibuprofen and diphenhydramine citrate were subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal, and photolytic degradation. Major unknown impurity formed under oxidative degradation was identified using LC-MS-MS study. The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of detection, limit of quantitation, accuracy, precision and robustness. The described method was linear over the range of 0.20-6.00 µg/mL (r>0.998) for Ibuprofen and 0.084-1.14 µg/mL for diphenhydramine citrate (r>0.998). The limit of detection results were ranged from 0.200-0.320 µg/mL for ibuprofen impurities and 0.084-0.099 µg/mL for diphenhydramine citrate impurities. The limit of quantitation results were ranged from 0.440 to 0.880 µg/mL for ibuprofen impurities and 0.258 to 0.372 µg/mL for diphenhydramine citrate impurities. The recovery of ibuprofen impurities were ranged from 98.1% to 100.5% and the recovery of diphenhydramine citrate impurities were ranged from 97.5% to 102.1%. This method is also suitable for the simultaneous assay determination of ibuprofen and diphenhydramine citrate in pharmaceutical dosage forms.