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, such as those of the oral cavity, esophagus, colon and rectum, and pancreas, as well as non-small cell lung cancers. The 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 product characterization necessitated the invention of a simpler, faster, and less expensive method. Therefore, this study aimed to follow the ICH method validation standards to develop and validate a fast, easy, and rugged liquid chromatography-mass spectrometry (LC-MS) technique for the concurrent estimation of tegafur, gimeracil, and oteracil potassium in the drug substance and the finished dosage form. Tegafur, gimeracil, and oteracil potassium were examined on the Waters HPLC Alliance system, coupled to the SCIEX QTRAP 5500 mass spectrometer, and endowed with an interface capable of carrying electrospray ionization. The tegafur, gimeracil, and oteracil peaks eluted at retention times of 2.338 min, 3.756 min, and 5.338 min, respectively. The limit of detection values of tegafur, gimeracil, and oteracil were detected to be 0.6, 0.174, and 0.474 μg/mL, respectively. The results for the quantification limit were calculated at 2.0, 0.58, and 1.58 µg/mL concentrations, respectively. Tegafur, gimeracil, and oteracil had linear ranges of 50-300 µg/ml, 14.5-87 µg/ml, and 39.5-237 µg/ml, with regression coefficients of 0.99956, 0.99986, and 0.999479, respectively. The accuracy values of tegafur, gimeracil, and oteracil in the ranges of 50%, 100%, and 150% were determined at 99.9%, 99.9%, and 99.4%, respectively. The RSD for the six replicates was less than 2% for precision. According to the ICH Q2 guidelines, this approach was effectively evaluated with LC-MS to validate the chemical structures of the 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 the drug material and the medicinal dosage form.