Meng Xiangjun, Xu Haitong, Zhang Zhi, Fawcett John Paul, Li Junru, Yang Yan, Gu Jingkai
School of Life Sciences, Jilin University, 2699 Qianjin Road, Changchun, Jilin, 130012, China.
School of Pharmacy, University of Otago, P.O. Box 56, Dunedin, 9054, New Zealand.
Anal Bioanal Chem. 2017 Aug;409(20):4885-4891. doi: 10.1007/s00216-017-0431-6. Epub 2017 Jun 28.
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.
利拉鲁肽是一种用于治疗2型糖尿病的胰高血糖素样肽-1类似物。利拉鲁肽生物分析中遇到的主要困难是人和动物血浆中的主要干扰以及串联质谱中的低片段信号。在本研究中,通过将差分离子淌度谱(DMS)与多离子监测检测(MIM)相结合,开发了一种液相色谱-差分离子淌度谱-串联质谱-多离子监测检测(LC-DMS-MIM)方法用于定量犬血浆中的利拉鲁肽。采用混合阴离子交换固相萃取进行样品制备。对DMS的参数进行了精心优化以提高分析物的信噪比。该测定法在1-100 ng/mL范围内呈线性,具有良好的准确度和精密度。该方法的定量下限(LLOQ,校准曲线上的最低标准)为1 ng/mL。研究表明,DMS是消除生物分析中干扰的有效工具,并且对于利拉鲁肽的生物分析,LC-DMS-MIM比经典的液相色谱-串联质谱(LC-MS/MS)具有更好的特异性和更高的信噪比。图形摘要 液相色谱-差分离子淌度谱-串联质谱-多离子监测检测法对利拉鲁肽进行生物分析的流程。