Stability of sterile saline solutions of synthetic tuftsin, a naturally occurring immunomodulating peptide.

Tuftsin, Thr-Lys-Pro-Arg, is a natural immunomodulating peptide originally found as a phagocytosis-stimulating factor for polymorphonuclear leukocytes. The peptide is now known to elicit various other activities including antimicrobial, antiviral and antitumor effects in vivo. Preliminary human studies revealed antitumor and anti-AIDS activities. In view of this clinical potential, we performed studies on the stability of sterile saline solutions of tuftsin stored at 25 degrees C, 5 degrees C, -20 degrees C or -70 degrees C utilizing a phagocytosis assay and analytical HPLC. Tuftsin stored at -20 degrees C or -70 degrees C gradually lost its phagocytosis-stimulating activity; tuftsin stored at 25 degrees C or 5 degrees C lost its phagocytosis activity rather rapidly. By 6 months, tuftsin stored at 25 degrees C lost all activity, and by 12 months, it significantly inhibited phagocytosis. In contrast, HPLC analysis indicated very minor changes. While tuftsin stored at 25 degrees C lost almost all activity by 6 months, we detected appearance of only 1% impurities by HPLC. This study indicates that if its activity is to be preserved, solutions of tuftsin must be frozen for storage.