https://scholars.lib.ntu.edu.tw/handle/123456789/484011
標題: | Development of a general method for quantifying IgG-based therapeutic monoclonal antibodies in human plasma using protein G purification coupled with a two internal standard calibration strategy using LC-MS/MS | 作者: | Chiu, Huai Hsuan Liao, Hsiao Wei YU-YUN SHAO YEN-SHEN LU CHING-HUNG LIN Tsai, I. Lin CHING-HUA KUO |
關鍵字: | Liquid chromatography-tandem mass spectrometry (LC-MS/MS) | Plasma | Post-column infusion internal standard (PCI-IS) | Protein G purification | Therapeutic monoclonal antibody (mAb);Liquid chromatography-tandem mass spectrometry (LC-MS/MS); Plasma; Post-column infusion internal standard (PCI-IS); Protein G purification; Therapeutic monoclonal antibody (mAb) | 公開日期: | 17-八月-2018 | 卷: | 1019 | 來源出版物: | Analytica Chimica Acta | 摘要: | © 2018 Elsevier B.V. Monoclonal antibody (mAb) drugs have generated much interest in recent years for treating various diseases. Immunoglobulin G (IgG) represents a high percentage of mAb drugs that have been approved by the Food and Drug Administration (FDA). To facilitate therapeutic drug monitoring and pharmacokinetic/pharmacodynamic studies, we developed a general liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify the concentration of IgG-based mAbs in human plasma. Three IgG-based drugs (bevacizumab, nivolumab and pembrolizumab) were selected to demonstrate our method. Protein G beads were used for sample pretreatment due to their universal ability to trap IgG-based drugs. Surrogate peptides that were obtained after trypsin digestion were quantified by using LC-MS/MS. To calibrate sample preparation errors and matrix effects that occur during LC-MS/MS analysis, we used two internal standards (IS) method that include the IgG-based drug-IS tocilizumab and post-column infused IS. Using two internal standards was found to effectively improve quantification accuracy, which was within 15% for all mAb drugs that were tested at three different concentrations. This general method was validated in term of its precision, accuracy, linearity and sensitivity for 3 demonstration mAb drugs. The successful application of the method to clinical samples demonstrated its’ applicability in clinical analysis. It is anticipated that this general method could be applied to other mAb-based drugs for use in precision medicine and clinical studies. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/484011 | ISSN: | 00032670 | DOI: | 10.1016/j.aca.2018.02.040 | SDG/關鍵字: | Column chromatography; Drug products; Mass spectrometry; Monoclonal antibodies; Patient monitoring; Plasma (human); Plasmas; Purification; Food and Drug Administration; Internal standards; Liquid chromatography tandem mass spectrometry (LC MS/MS); Monoclonal antibodies (mAb); Protein G; Sample pretreatment; Therapeutic drug monitoring; Therapeutic monoclonal antibodies; Liquid chromatography; bevacizumab; immunoglobulin G; immunoglobulin G1; monoclonal antibody; nivolumab; pembrolizumab; protein G; tocilizumab; immunoglobulin G; accuracy; amino acid sequence; Article; blood sampling; calibration; controlled study; drug efficacy; drug purification; drug selectivity; hydrophobicity; liquid chromatography; mass spectrometry; priority journal; protein purification; proton transport; retention time; validity; blood; human; isolation and purification; liquid chromatography; tandem mass spectrometry; Calibration; Chromatography, Liquid; Humans; Immunoglobulin G; Tandem Mass Spectrometry |
顯示於: | 腫瘤醫學研究所 |
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