TY - JOUR
T1 - A validated bioanalytical HPLC method for pharmacokinetic evaluation of 2-deoxyglucose in human plasma
AU - Gounder, Murugesan K.
AU - Lin, Hongxia
AU - Stein, Mark
AU - Goodin, Susan
AU - Bertino, Joseph R.
AU - Kong, Ah Ng Tony
AU - Dipaola, Robert S.
PY - 2012/5
Y1 - 2012/5
N2 - 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 45min. 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 425nm. The 2-DG calibration curves were linear over the range of 0.63-300μg/mL with a limit of detection of 0.5μg/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.
AB - 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 45min. 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 425nm. The 2-DG calibration curves were linear over the range of 0.63-300μg/mL with a limit of detection of 0.5μg/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.
KW - 2-deoxyglucose
KW - Fluorescence derivatization
KW - HPLC
KW - Pharmacokinetics
UR - https://www.scopus.com/pages/publications/84859439369
UR - https://www.scopus.com/inward/citedby.url?scp=84859439369&partnerID=8YFLogxK
U2 - 10.1002/bmc.1710
DO - 10.1002/bmc.1710
M3 - Article
C2 - 21932382
AN - SCOPUS:84859439369
SN - 0269-3879
VL - 26
SP - 650
EP - 654
JO - Biomedical Chromatography
JF - Biomedical Chromatography
IS - 5
ER -