title: Trans-3,4-dideoxyglucone-3-ene (trans-3,4-DGE), a most reactive glucose degradation product in freshly heat sterilized glucose solutions.
abstract: 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 β-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 trans-3,4-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.
authors.affiliation: Global Formulation Research-US, Eisai Inc., 900 Davis Drive, RTP, NC 27709, USA. Electronic address: kechen24@yahoo.com.
authors.forename: Ke
authors.initials: K
authors.lastname: Chen
authors.affiliation: Global Formulation Research-US, Eisai Inc., 900 Davis Drive, RTP, NC 27709, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Prabel
authors.affiliation: Global Formulation Research-US, Eisai Inc., 900 Davis Drive, RTP, NC 27709, USA.
authors.forename: Johanna
authors.initials: J
authors.lastname: Dutton
authors.affiliation: Analytical Research Laboratory, Eisai Co., Ltd., 1-3, Tokodai 5-Chome, Tsukuba, Ibaraki 300-2635, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Gotoda
authors.affiliation: Analytical Research Laboratory, Eisai Co., Ltd., 1-3, Tokodai 5-Chome, Tsukuba, Ibaraki 300-2635, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Asai
authors.affiliation: Global Formulation Research-US, Eisai Inc., 900 Davis Drive, RTP, NC 27709, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Grobin
mesh_terms: D005947:Glucose / Q000737:chemistry*; D006358:Hot Temperature; D008968:Molecular Conformation; D008970:Molecular Weight; D011753:Pyrones / Q000737:chemistry*; D012996:Solutions; D013237:Stereoisomerism; D013242:Sterilization
chemical_list: C504711:3,4-dideoxyglucosone-3-ene; D011753:Pyrones; D012996:Solutions; D005947:Glucose
keywords: Acetoacetanilide derivative; Dinitrophenylhydrazine (DNPH) derivative; Glucose degradation products (GDPs); Trans-3,4-dideoxyglucosone-3-ene (trans-3,4-DGE)