Determination of metformin in mouse, rat, dog and human plasma samples by laser diode thermal desorption/atmospheric pressure chemical ionization tandem mass spectrometry.
A simple, rapid and robust high-throughput assay for the quantitative analysis of metformin in plasma from different species using laser diode thermal desorption interfaced with atmospheric chemical pressure ionization tandem mass spectrometry (LDTD-APCI-MSMS) was developed for use in a pharmaceutical discovery environment. In order to minimize sample preparation a generic protein precipitation method was used to extract metformin from the plasma. Laser diode thermal desorption is a relatively new sample introduction method, the optimization of the instrumental parameters are presented. The method was successfully applied to spiked mouse, rat, dog and human plasma samples and was subsequently used to determine the oral pharmacokinetics of metformin after dosing to male rats in order to support drug discovery projects. The deviations for intra-assay accuracy and precision across the four species were less than 30% at all calibration and quality control levels.
Swales
John G
JG
Astrazeneca R&D, DxDMPK CVGI RA, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK. john.swales@astrazeneca.com
Gallagher
Richard
R
Peter
Raimund M
RM
D000818:Animals; D001274:Atmospheric Pressure; D004285:Dogs; D057166:High-Throughput Screening Assays; D006801:Humans; D007004:Hypoglycemic Agents / Q000097:blood*; D054023:Lasers, Semiconductor; D008297:Male; D008687:Metformin / Q000097:blood*; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D053719:Tandem Mass Spectrometry / Q000379:methods*
D007004:Hypoglycemic Agents; D008687:Metformin