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

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-mass

spectrometry (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 5500 mass spectrometer endowed with an interface capable of

carryout 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 (LOD) values of

tegafur, gimeracil, and oteracil were detected to be 0.6, 0.174, and 0.474 μg/mL, respectively

however the results for quantification limit (LOQ) were calculated to be 2.0, 0.58, 1.58 µg/mL

concentration, respectively. Tegafur, gimeracil, and oteracil had linear ranges of 50-300 µg/ml,

14.5-87 µg/ml, and 39.5-237 µg/ml, respectively, with regression coefficients of 0.99956, 0.99986,

and 0.999479. Accuracy values for tegafur, gimeracil, and oteracil in the ranges of 50%, 100%

and 150% for each were respectively, were determined to be 99.9%, 99.9%, and 99.4%. The %

RSD for six replicates was less than 2% for precision. According to ICH Q2 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.