Trans-3,4-dideoxyglucone-3-ene (trans-3,4-DGE), a most reactive glucose degradation product in freshly heat sterilized glucose solutions

摘要

In our study, one or more glucose degradation products (GDPs) in freshly heat sterilized dextrose 5% in water (D5W) were found to react with a drug candidate having a beta-keto amide group (Compound A) to form several drug related compounds with the same molecular weight. However the previously identified GDPs did not react with Compound A to produce the observed adducts, indicating that unidentified GDP(s) reacted with Compound A to form these adducts. Our investigation by reaction-directed fractionation of the reactive D5W with HPLC led to the identification of the reactive GDP, trans-3,4-dideoxyglucosone- 3-ene (trans-3,4-DGE), responsible for producing these reaction products. The trans3,4- DGE was identified from its derivatives of dinitrophenylhydrazine (DNPH) and acetoacetanilide and confirmed by (1) admixing Compound A with authentic trans-3,4-DGE to produce the identical impurities as admixing with freshly heat sterilized D5W, and (2) NMR analysis of the reactive fraction of glucose solutions. (C) 2015 Elsevier Ltd. All rights reserved.