Ultra-high pressure liquid chromatography-tandem mass spectrometry method for the determination of omarigliptin in rat plasma and its application to a pharmacokinetic study in rats.
Omarigliptin is a novel long-acting dipeptidyl peptidase-4 inhibitor used for the treatment of type 2 diabetes. In this work, a sensitive and selective ultra-high pressure liquid chromatography tandem mass spectrometry method was developed and validated for the determination of omarigliptin in rat plasma. Sample preparation was performed by protein precipitation with acetonitrile. Chromatographic separation of analytes was achieved on an RRHD Eclipse Plus C18 column (2.1 × 50 mm, 1.8 μm), using gradient mobile phase (0.1% formic acid-acetonitrile) at a flow rate of 0.4 mL/min. Detection was performed in multiple reaction monitoring mode, with target fragment ions m/z 399.1 → 152.9 for omarigliptin and m/z 237.1 → 194 for the internal standard. The total run time was 4 min. Retention time of omarigliptin and internal standard was 1.25 and 2.12 min, respectively. Relative standard deviation (%) of the intra- and inter-day precision was below 10.0%, and accuracy was between 97.9% and 105.3%. Calibration curve was established over the range 2-5000 ng/mL with good linearity. The lower limit of quantification and limit of detection of omarigliptin were 2 and 0.25 ng/mL, respectively. Mean recoveries were in the range 87.3-95.1% for omarigliptin. No matrix effect was observed in this method. This novel method has been successfully applied to a pharmacokinetic study of omarigliptin in rats. The absolute bioavailability of omarigliptin was identified as high as 87.31%.
Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, China.|Key Laboratory of Molecular Cardiology, Shaanxi Province, China.|Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, China.
Meng-Fang
http://orcid.org/0000-0002-4759-2619
MF
Li
School of Pharmacy of Wenzhou Medical University, China.
Xiao-Xia
XX
Hu
Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, China.|Key Laboratory of Molecular Cardiology, Shaanxi Province, China.|Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, China.
Ai-Qun
AQ
Ma
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D006574:Heterocyclic Compounds, 2-Ring / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D057230:Limit of Detection; D016014:Linear Models; D008297:Male; D011714:Pyrans / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
C587539:2-(2,5-difluorophenyl)-5-(2-(methylsulfonyl)-2,6-dihydropyrrolo(3,4-c)pyrazol-5(4H)-yl)tetrahydro-2H-pyran-3-amine; D006574:Heterocyclic Compounds, 2-Ring; D011714:Pyrans
Omarigliptin; UHPLC-MS/MS; pharmacokinetics; rat plasma