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

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Abstract

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.

Process for the bioanalysis of liraglutide by liquid chromatography differential mobility spectrometry tandem mass spectrometry with multiple ion monitoring detection

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Acknowledgments

The authors gratefully acknowledge financial support from the National Natural Science Foundation of China (Grant Nos. 81430087, 81473142, 81673396, and 81673502). We are also grateful to SCIEX application engineers Huaidong Yu and Chao Zhang for technical support.

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Authors and Affiliations

  1. School of Life Sciences, Jilin University, 2699 Qianjin Road, Changchun, Jilin, 130012, China

    Xiangjun Meng, Haitong Xu, Zhi Zhang, Junru Li, Yan Yang & Jingkai Gu

  2. School of Pharmacy, University of Otago, P.O. Box 56, Dunedin, 9054, New Zealand

    John Paul Fawcett

  3. Clinical Pharmacology Center, Research Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, Jilin, 130061, China

    Jingkai Gu

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  1. Xiangjun Meng
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  2. Haitong Xu
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  4. John Paul Fawcett
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  5. Junru Li
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  6. Yan Yang
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Correspondence to Yan Yang or Jingkai Gu.

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Meng, X., Xu, H., Zhang, Z. et al. Differential mobility spectrometry tandem mass spectrometry with multiple ion monitoring for the bioanalysis of liraglutide. Anal Bioanal Chem 409, 4885–4891 (2017). https://doi.org/10.1007/s00216-017-0431-6

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  • DOI: https://doi.org/10.1007/s00216-017-0431-6

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