Validated LC-MS/MS methods for the determination of dapagliflozin, a sodium-glucose co-transporter 2 inhibitor in normal and ZDF rat plasma.
BACKGROUND
Dapagliflozin is an inhibitor of sodium-glucose co-transporter 2 (SGLT-2) in development for the treatment of Type 2 diabetes. To support toxicology studies, LC-MS/MS methods were developed and validated for the quantitation of dapagliflozin in rat plasma.


RESULTS
The assay uses solid phase extraction and LC-MS/MS analysis in negative ion electrospray ionization mode. Because dapagliflozin readily forms adducts in the presence of formic acid, the mobile phases were simple mixtures of water and acetonitrile. The assay was validated in the concentration range of 5-2000 ng/ml with good intra- and inter-day precisions and acceptable sample stability.


CONCLUSIONS
The validated assay was successfully applied to the quantitation of dapagliflozin in plasma in support of preclinical studies in both normal and diabetic rats.
Bristol-Myers Squibb, Bioanalytical Sciences, Route 206 and Province Line Road, Princeton, NJ, USA. anne.aubry@bms.com
Anne-Françoise
AF
Aubry
Huidong
H
Gu
Reynald
R
Magnier
Ling
L
Morgan
Xiaohui
X
Xu
Mark
M
Tirmenstein
Bonnie
B
Wang
Yuzhong
Y
Deng
Jinnan
J
Cai
Philippe
P
Couerbe
Mark
M
Arnold
D000097:Acetonitriles / Q000737:chemistry; D000818:Animals; D001559:Benzhydryl Compounds; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000097:blood* / Q000378:metabolism; D005960:Glucosides / Q000097:blood* / Q000378:metabolism; D013058:Mass Spectrometry / Q000379:methods*; D051381:Rats; D011924:Rats, Zucker; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D052616:Solid Phase Extraction / Q000379:methods; D014867:Water / Q000737:chemistry
D000097:Acetonitriles; D001559:Benzhydryl Compounds; D004791:Enzyme Inhibitors; D005960:Glucosides; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D014867:Water; C529054:dapagliflozin; C032159:acetonitrile