In this editorial, Robert MacNeill (Envigo) dicusses the case for the surrogate analyte approach for biomarker validation.
Poster: an immunoaffinity capture/UPLC-MS/MS method for multiplexed quantitation of two highly homologous antibodies in human serum
Monoclonal antibody (mAb) based biotherapeutics have emerged as a dominant class of approved medicines during the past decade in both market share and variety of target diseases. Ligand binding assays (LBAs), such as enzyme-linked immunosorbent assays (ELISA), have been the gold standard for the bioanalysis of mAbs in support of non-clinical and clinical trials. While conventional LBAs provide highly sensitive and specific detection for the quantitation of mAbs, combining an LBA with liquid chromatography tandem mass spectrometry (LC-MS/MS) detection offers additional orthogonal dimensions of selectivity/specificity, extending the assay utility to a multiplexed format otherwise not achievable by LBA alone.
To date, almost all protein LC-MS/MS based bioanalysis has involved the use of trypsin to cleave biopharmaceuticals into manageable peptides for quantitation. In some cases, where trypsin does not generate useful peptide sequences, a different cleavage agent is required. Glu-C is an enzyme that is frequently used for protein characterisation, and cuts proteins on the C-terminal side of the aspartic and glutamic acid residues. These two molecules are acidic amino acids, whereas the ubiquitous trypsin cleaves at the basic residues (lysine and arginine), therefore making this an orthogonal cleavage enzyme.
In this application note, Yun Alelyunas (Waters Corporation) describes an LC-HRMS method for high sensitivity bioanalysis of monoclonal antibodies by direct mass measurement at the intact level for whole molecule quantification. This emerging approach can serve as an alternative or complement to traditional methods such as ligand binding assay for protein quantification. Methodology and guidance for evaluating and optimizing data processing parameters are discussed in detail.
Waters’ team of bioanalysis experts developed the Peptide & Protein Bioanalysis Boot Camp – a…
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A targeted, sensitive, robust, reliable and cost-effective workflow for quantitation of biologics
In this installment of Robert MacNeill’s (Envigo) column, Robert discusses the instability of drugs within samples and how to balance their instability against absorptive loss.
The validation of an LC–MS/MS assay for perhexiline and major hydroxy metabolites, and its application to therapeutic monitoring in patient plasma
In this research article an LC–MS/MS method, using two novel internal standards, has been validated for the quantitative measurement of PEX and its major hydroxy metabolites in human plasma.
Nightingale Health (Vantaa, Finland) have obtained the CE marking for their blood biomarker analysis platform.
Current thinking on quantification of protein therapeutic pharmacokinetics and protein biomarkers in clinical studies
In this commentary, Kate Peng discusses the current thinking on quantification of protein therapeutic pharmacokinetics and protein biomarkers in clinical studies.