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Simultaneous quantitative determination of liraglutide and insulin degludec in rat plasma by liquid chromatography–tandem mass spectrometry method and its application
Authors:Jianping Zhai  Li Li  Lihou Dong  Kelly Dong  Shensi Xiang  Luolan Gui  Jiaying Zhang  Haifeng Song  Zhiqiang Ge
Institution:1. School of Chemical Engineering, Tianjin University, Tianjin, China;2. State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of LifeOmics, Beijing, China

Beijing United-Power Pharma Tech Co., Ltd., Beijing, China;3. State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of LifeOmics, Beijing, China;4. Beijing United-Power Pharma Tech Co., Ltd., Beijing, China

Abstract:A simple, fast and high-throughput LC–tandem mass spectrometry method was developed and validated to simultaneously measure liraglutide and insulin degludec in rat plasma. After protein precipitation, plasma samples were subjected to gradient elution using an InertSustain Bio C18 column with 1000/20/1 water/acetonitrile/formic acid (v/v/v) and 1000/1 acetonitrile/formic acid (v/v) as the mobile phase. The method was validated from 1.00 to 500 ng/mL of liraglutide and insulin degludec. Further, the extraction recovery from the plasma was 41.8%–49.2% for liraglutide and 56.5%–69.7% for insulin degludec. Intra- and inter-day precision of liraglutide was 3.5%–9.4% and 8.4%–9.8%, respectively, whereas its accuracy was between −12.6% and −1.3%. Intra- and inter-day precision of insulin degludec was 5.2%–13.6% and 11.8%–19.1%, respectively, showing an accuracy between −3.0% and 9.9%. As a result, the method was successfully applied to a pharmacokinetics study of liraglutide and insulin degludec following a single-dose subcutaneous administration to rats.
Keywords:insulin degludec  liquid chromatography–tandem mass spectrometry  liraglutide  pharmacokinetics
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