Differential mobility spectrometry tandem mass spectrometry with multiple ion monitoring for the bioanalysis of liraglutide

• Published in: Analytical and bioanalytical chemistry Vol. 409; no. 20; pp. 4885 - 4891
• Main Authors: Meng, Xiangjun, Xu, Haitong, Zhang, Zhi, Fawcett, John Paul, Li, Junru, Yang, Yan, Gu, Jingkai
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.08.2017; Springer Nature B.V
• Subjects: Analytical Chemistry; Animals; anion exchange; Anion exchanging; Antidiabetics; Biochemistry; Characterization and Evaluation of Materials; Chemistry; Chemistry and Materials Science; Chromatography; Diabetes mellitus; Dogs; Food Science; Glucagon; Glucagon-like peptide 1; humans; Hypoglycemic Agents - analysis; Interference; Ions; Laboratory Medicine; Limit of Detection; Liquid chromatography; Liraglutide - chemistry; Mass spectrometry; Mass spectroscopy; Mobility; Monitoring; Monitoring/Environmental Analysis; noninsulin-dependent diabetes mellitus; Quantitation; Reproducibility of Results; Research Paper; Sample preparation; Scientific imaging; Signal to noise ratio; solid phase extraction; Spectroscopy; tandem mass spectrometry; Tandem Mass Spectrometry - methods; Mixed anion-exchange; Differential mobility spectrometry; Multiple ion monitoring; Liraglutide
• ISSN: 1618-2642; 1618-2650; 1618-2650
• DOI: 10.1007/s00216-017-0431-6

Liraglutide is a glucagon-like peptide-1 analog for the treatment of type 2 diabetes. Major interference in plasma of human and animals and low fragment signal in tandem mass spectrometry are the main difficulties encountered in the bioanalysis of liraglutide. In this study, by combining differential mobility spectrometry (DMS) with multiple ion monitoring detection (MIM), a liquid chromatography differential mobility spectrometry tandem mass spectrometry with multiple ion monitoring detection (LC-DMS-MIM) method was developed for the quantitation of liraglutide in dog plasma. Mixed anion-exchange solid-phase extraction was used for sample preparation. The parameters of DMS were meticulously optimized to increase the signal-to-noise ratio of the analyte. The assay was linear in the range 1–100 ng/mL with good accuracy and precision. The lower limit of quantitation (LLOQ, the lowest standard on the calibration curve) of this method was 1 ng/mL. The research reveals that DMS is an effective tool for the elimination of interference in bioanalysis and that LC-DMS-MIM has better specificity and higher signal-to-noise ratio than classical liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the bioanalysis of liraglutide. Graphical abstract Process for the bioanalysis of liraglutide by liquid chromatography differential mobility spectrometry tandem mass spectrometry with multiple ion monitoring detection