title: Simultaneous quantitation of metformin and sitagliptin from mouse and human dried blood spots using laser diode thermal desorption tandem mass spectrometry.
abstract: A simple, rapid and robust high-throughput assay for the simultaneous analysis of metformin and sitagliptin from mouse and human dried blood spot samples using laser diode thermal desorption interfaced with atmospheric pressure chemical ionization tandem mass spectrometry (LDTD-APCI-MS/MS) was developed for use in a pharmaceutical discovery environment as an alternative to traditional plasma analysis. Analytes were extracted from dried blood spots using a simple punch disc and solvent extract procedure. Details of the method development and optimization of the instrumental parameters are presented. The method was successfully applied to spiked mouse and human dried blood spot samples. Analyte stability was determined in dried blood spots on FTA cards and as extracts of dried blood spots. The method was subsequently used to determine the oral pharmacokinetics of metformin and sitagliptin after dosing to male mice. Metformin and Sitagliptin results are compared to data generated by more traditional liquid chromatography-mass spectrometry methods. Intra-assay and inter-assay accuracy and precision across the analytes and species deviated by less than 30% at all calibration levels and less than 20% at all quality control levels.
authors: AstraZeneca, Discovery Drug Metabolism and Pharmacokinetics, Cardiovascular & Gastrointestinal Research Area, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK. john.swales@astrazeneca.com
authors: John G
authors: JG
authors: Swales
authors: Richard T
authors: RT
authors: Gallagher
authors: Mark
authors: M
authors: Denn
authors: Raimund M
authors: RM
authors: Peter
mesh_terms: D000818:Animals; D001801:Blood Stains; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods; D004355:Drug Stability; D004356:Drug Storage; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000097:blood*; D054023:Lasers, Semiconductor; D008687:Metformin / Q000008:administration & dosage / Q000097:blood*; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D011719:Pyrazines / Q000008:administration & dosage / Q000097:blood*; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D000068900:Sitagliptin Phosphate; D013045:Species Specificity; D013048:Specimen Handling; D053719:Tandem Mass Spectrometry; D013696:Temperature; D014230:Triazoles / Q000008:administration & dosage / Q000097:blood*
chemical_list: D007004:Hypoglycemic Agents; D011719:Pyrazines; D014230:Triazoles; D008687:Metformin; D000068900:Sitagliptin Phosphate