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. |
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