Development and validation of a stability-indicating RP-HPLC method for the identification, determination of related substances and assay of dimethyl fumarate in drug substance

Abstract

The objective of current study was to develop and validate a short, economical, accurate, precise stability-indicating RP-HPLC method for identification, quantitation of related substances (fumaric acid and mono methyl fumarate) and assay of dimethyl fumarate (DMF) drug substance. The RP-HPLC method was developed by using liquid chromatography (waters 2695 with PDA detector & Agilent 1200 with DAD) with Symmetry C18 column. Pharmaceutical grade of high pure materials of DMF, MMF, FA and HPLC grade water, acetonitrile and orthophosphoric acid were used for this study. The mobile phase consists of 0.1% of ortho-phosphoric acid in water: acetonitrile (55:45% v/v). The developed method was validated according to ICH guidelines. To prove the stability indicating potential, stress studies performed using acid, base, peroxide and thermal. After sufficient exposure, these solutions were injected in to HPLC and found that all degradants formed during stress study were well separated from the main peak and resolution between all impurities was more than ICH requirements. A simple, short and stability indicating RP-HPLC method was developed and validated for simultaneous estimation of DMF and its related substances in drug substance. Based on literature survey it was evident that many methods were published for determination of DMF individually or its related substances, however short run time methods were not available for simultaneous estimation of DMF and its related substances. The intended method would support to industries for quick quantitation of DMF and its related substances without compromising quality parameters like precision and accuracy.