The C-terminal octapeptide of cholecystokinin (CCK8) includes some easily oxidizable amino acids. The oxidation of CCK8 by reactive oxygen species (ROS) such as hydrogen peroxide (H(2)O(2)) and hydroxyl radicals (OH(*)) was investigated using reversed-phase high performance liquid chromatography (RP-HPLC) and subsequent electrospray ionization mass spectrometry. The mechanism of oxidation of CCK8 in the H(2)O(2) system differed from that of CCK8 in the Fenton system, in which OH(*) are produced. In the H(2)O(2) system, (28)Met and (31)Met were oxidized to methionine sulfoxide, and no further oxidation or degradation/hydrolysis occurred. On the other hand, in the Fenton system, (28)Met and (31)Met residues were oxidized to methionine sulfone via the formation of methionine sulfoxide. In addition, the oxidized product was observed at the Trp residue but not at the Tyr residue, and small peptide fragments from CCK8 were observed in the Fenton system. From these results, it was concluded that (28)Met and (31)Met residues of CCK8 are susceptible to oxidation by ROS.

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TS-1 is an oral anticancer agent comprising three components: two biochemical modulators of 5-fluorouracil (5-FU) and tegafur (FT), a prodrug of 5-FU. TS-1 displays potent anti-tumor activity by maintaining effective 5-FU concentrations in serum for a prolonged period. FT is gradually converted to 5-FU in vivo via 5'-hydroxylation mediated by cytochrome P450s. As a result, genetic polymorphisms can cause wide individual differences in serum concentration of 5-FU after administration of TS-1, requiring monitoring of serum concentration of 5-FU for each patient. Chemotherapy with TS-1 plays a major role in the treatment of oral cancer. In cases where a patient with oral cancer shows dysphagia, TS-1 may need to be tube-administered. Although tube administration by the simple suspension method has been recommended from a biosafety perspective, particularly for anti-cancer agents, its efficacy remains unclear. We established a simple high-performance liquid chromatography method for simultaneous determination of FT and 5-FU levels at clinical sites by modifying a method reported in the literature.1) Unlike the original method, this simplified method does not require extraction procedures to separate FT and 5-FU, and requires only 250 µl of serum. Using this method, we compared FT concentrations in the sera of oral cancer patients administered TS-1 orally or via a tube-assisted simple suspension method. No significant differences in FT concentrations were apparent between these two modes of administration. TS-1 treatment by tube administration using the simple suspension method thus seems useful for patients with dysphagia as an alternative to oral dosage.