Stability prediction of nafamostat mesilate in an intravenous admixture containing sodium bisulfite.
The hydrolysis of nafamostat mesilate (NM) in aqueous solution was found to be accelerated by sodium bisulfite (SBS) using high-performance liquid chromatographic assay. The hydrolysis of NM catalyzed by SBS was pseudo-first-order and was considered to be a reaction between nafamostat cation (N+) and sulfite ion. The effects of SBS concentration and temperature on the hydrolysis of NM in buffer solution were examined. From the findings obtained, we estimated the compatible pH range of the intravenous admixture (mixed infusion) of NM after a constant storage time at a constant SBS concentration and temperature employing a simulated pH-profile for the mixed infusion. In order to evaluate the compatibility of the prescribed mixed infusion, the method of pH estimation for the mixed infusion was also investigated using the pH titration curve of each preparation.
Asahara
K
K
Department of Pharmacy, Hyogo Prefectural Kaibara Hospital, Japan.
Yamada
H
H
Yoshida
S
S
Hirose
S
S
D001550:Benzamidines; D004355:Drug Stability; D006146:Guanidines / Q000008:administration & dosage / Q000032:analysis*; D007275:Injections, Intravenous; D013447:Sulfites
D001550:Benzamidines; D006146:Guanidines; D013447:Sulfites; C009279:sodium bisulfite; C032855:nafamostat