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
Journal
Analytica Chimica Acta
Journal Volume
1019
Date Issued
2018-08-17
Author(s)
Abstract
© 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.
Subjects
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)
SDGs
Other Subjects
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
Type
journal article