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Poster Presentations
Day 4, June 25（Wed.）
Room P (Maesato East, Foyer, Ocean Wing)
- 4P-AM-19
Fundamental study of a simultaneous analytical method of pyrimidine bases and metabolites using liquid chromatography/tandem mass spectrometry
(1Tohoku Univ., 2Tohoku Univ. Hosp., 3INGEM., Tohoku Univ.)
oMidori Kato1, Masamitsu Maekawa1,2,3, Eiji Hishinuma3, Masahiro Hiratsuka1,2,3, Nariyasu Mano1,2
Although fluoropyrimidine anticancer drug (FP) is majorly used, severe adverse effects (AE) have occurred in approximately 30% of patients. It is reported that deficiencies of enzyme activities involved in FP metabolism, such as dihydropyrimidine dehydrogenase (DPD), dihydropyrimidinase, and beta-ureidopropionase, enzymes increase risks of AE. These enzymes also metabolize endogenous pyrimidine bases. We predicted they can be surrogate biomarkers for avoiding AE, and therefore, started to develop the simultaneous LC/MS/MS method for measuring 8 endogenous pyrimidine bases and the metabolites. The former method we developed, sensitivity and reproducibility of uracil and β-alanine were insufficient. Therefore, we have tried liquid-liquid extraction (LLE) pretreatment and dansyl chloride (DNS-Cl) derivatization.
As a result, DNS-Cl derivatization made analysis of uracil and β-alanine more sensitive. The signal-to-noise ratio of uracil was 14 times, and the sensitivity of β-alanine was twice higher than that of underivatized compounds. For derivatization method, 30 min for reaction time and pH 12 was suitable. NaHCO3 was appropriate rather than NaOH. These results suggested to the possibility of detecting the compounds in plasma by combination of LLE pretreatment and DNS-Cl derivatization. In the future, we are going to analyze patient samples and investigate the correlation between these biomarkers and adverse effects information.