Characterization of forced degradants of Tegafur, Gimeracil, and Oteracil potassium by Liquid Chromatographic-Electrospray Ionization-Mass Spectrometry and simultaneous estimation of triple combination in drug substance and finished pharmaceutical Dosage Form

Tegafur, gimeracil, and oteracil potassium are widely used pharmaceuticals to treat lung cancers of the gastrointestinal tract like the oral cavity, esophagus, colon and rectum, pancreas, and also non-small cell lung cancers. Literature review revealed that no study has yet offered a completely stability-demonstrating, validated liquid chromatography-mass spectrometric approach for the concurrent estimation of tegafur, gimeracil, and oteracil potassium along with all known degradation products. The simultaneous detection of tegafur, gimeracil, and oteracil potassium, and their forced degradation products characterization, necessitated the invention of a simple, faster, and less expensive method. The goal of the study was to follow ICH method validation standards to develop and validate a fast, easy, and rugged liquid chromatography-massspectrometry (LC-MS) technique for the concurrent estimation of Tegafur, gimeracil, and oteracil potassium in drug substance and finished dosage form according to ICH method validation guidelines. Tegafur, gimeracil, and oteracil potassium were examined on Waters HPLC Alliance system coupled to SCIEX QTRAP ۵۵۰۰ mass spectrometer endowed with an interface capable ofcarryout electrospray ionization. The tegafur, gimeracil, and oteracil peaks eluted at retention times of ۲.۳۳۸ min., ۳.۷۵۶ min., and ۵.۳۳۸ min. respectively. The limit of detection (LOD) values oftegafur, gimeracil, and oteracil were detected to be ۰.۶, ۰.۱۷۴, and ۰.۴۷۴ μg/mL, respectively however the results for quantification limit (LOQ) were calculated to be ۲.۰, ۰.۵۸, ۱.۵۸ µg/mLconcentration, respectively. Tegafur, gimeracil, and oteracil had linear ranges of ۵۰-۳۰۰ µg/ml, ۱۴.۵-۸۷ µg/ml, and ۳۹.۵-۲۳۷ µg/ml, respectively, with regression coefficients of ۰.۹۹۹۵۶, ۰.۹۹۹۸۶, and ۰.۹۹۹۴۷۹. Accuracy values for tegafur, gimeracil, and oteracil in the ranges of ۵۰%, ۱۰۰% and ۱۵۰% for each were respectively, were determined to be ۹۹.۹%, ۹۹.۹%, and ۹۹.۴%. The % RSD for six replicates was less than ۲% for precision. According to ICH Q۲ guidelines, this approach was effectively evaluated with LC-MS to validate the chemical structures of freshly created tegafur, gimeracil, and oteracil degradation products. An accurate and sensitive LC-MS technique was developed and validated for the concurrent quantification of tegafur, gimeracil, and oteracil potassium in drug material and medicinal dosage form.