title: A validated bioanalytical HPLC method for pharmacokinetic evaluation of 2-deoxyglucose in human plasma.
abstract: 2-Deoxyglucose (2-DG), an analog of glucose, is widely used to interfere with glycolysis in tumor cells and studied as a therapeutic approach in clinical trials. To evaluate the pharmacokinetics of 2-DG, we describe the development and validation of a sensitive HPLC fluorescent method for the quantitation of 2-DG in plasma. Plasma samples were deproteinized with methanol and the supernatant was dried at 45°C. The residues were dissolved in methanolic sodium acetate-boric acid solution. 2-DG and other monosaccharides were derivatized to 2-aminobenzoic acid derivatives in a single step in the presence of sodium cyanoborohydride at 80°C for 45 min. The analytes were separated on a YMC ODS C₁₈ reversed-phase column using gradient elution. The excitation and emission wavelengths were set at 360 and 425 nm. The 2-DG calibration curves were linear over the range of 0.63-300 µg/mL with a limit of detection of 0.5 µg/mL. The assay provided satisfactory intra-day and inter-day precision with RSD less than 9.8%, and the accuracy ranged from 86.8 to 110.0%. The HPLC method is reproducible and suitable for the quantitation of 2-DG in plasma. The method was successfully applied to characterize the pharmacokinetics profile of 2-DG in patients with advanced solid tumors.
authors.affiliation: The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08901, USA. goundemk@umdnj.edu
authors.forename: Murugesan K
authors.initials: MK
authors.lastname: Gounder
authors.forename: Hongxia
authors.initials: H
authors.lastname: Lin
authors.forename: Mark
authors.initials: M
authors.lastname: Stein
authors.forename: Susan
authors.initials: S
authors.lastname: Goodin
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Bertino
authors.forename: Ah-Ng Tony
authors.initials: AN
authors.lastname: Kong
authors.forename: Robert S
authors.initials: RS
authors.lastname: DiPaola
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003847:Deoxyglucose / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D004355:Drug Stability; D005456:Fluorescent Dyes; D006801:Humans; D057230:Limit of Detection; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D000964:Antimetabolites, Antineoplastic; D005456:Fluorescent Dyes; D003847:Deoxyglucose