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L-4-oxalysinyl-norvalinyl-N3-4-methoxyfumaroyl-L-2,3-diaminopropanoic acid (I-677-Nva-FMDP) is a new tripeptide synthesized in our group. This peptide exhibits potent anticandida Albicans activity. In the presence of serum, the antifun gal activity of I-677-Nva-FMDP decreases after incubating over 1h. In order to investigate the relationship between the degradation and antifungal activity of I-677-Nva-FMDP, the concentrations of I-677-Nva-FMDP and N3-methoxyfumaroyl-L-2,3-diaminopropanoic acid (FMDP) were determined at different incubating time in mice serum. The incubating time range was from 0 to 300 min and the incubating samples were measured at intervals of 30 min. For this measurement reversed-phase HPLC was used and the mobile phase was composed of 8% methanol and 0.1% trifluoroacitic acid-triethyl amine buffer (pH 3). In this condition the retention time of FMDP and I-677-Nva-FMDP were 3.9 min and 16.5 min respectively. Methanol was superior to other reagents for the removal of protein from the incubating medium and there was not any interference peak before the retention time of I-677-Nva-FMDP. A decrease in concentration of I-677-Nva-FMDP was observed from 0 min to 180 min and no I-677-Nva-FMDP could be detected at 210 min whereas the concentration of FMDP incresed from 30 min to 2h and reached a maximum at 120 min. The results showed that the half life (t1/2) of I-677-Nva-FMDP was 70 min. This result coincided with the antifungal test in vitro.