A Multiplexed Hybrid LC–MS/MS Pharmacokinetic Assay to Measure Two Co-Administered Monoclonal Antibodies in A Clinical Study

Abstract

The multiplexed LC-MS/MS method provided a powerful quantitative tool for clinical PK assessment of co-administered mAbs without the requirement for stringent affinity capture reagents.

Targeted LC-MS Quantification of Intact Tat-Fusion Therapeutics: A Case Study

“…The primary charge states from 4+ to 8+ with the most intense peak observed at 6+. This distribution pattern was roughly in consistent with the estimation by the charged residue model and Rayleigh equation [12]. In addition, a series of peak with a mass increment of around 98 Da was detected as well (Figure 2A).…”

“…LC-MS has emerged as a promising alternative for fusion protein/polypeptide quantification in biological matrices, because it provides high specificity, high sensitivity and multiplexing capability and is often not matrix-selective. By performing proteolysis and monitoring MS-favorable signature peptide(s), LC-MS usually achieves better (or comparable) performance to immunoassays [7][8][9][10][11][12]. Nevertheless, this peptide-centered analysis may not be directly applicable to the pharmacokinet- 10.4155/BIO.…”

Recommendations for Validation of LC-MS/MS Bioanalytical Methods for Protein Biotherapeutics

“…LC-MS/MS assays have been reported for the determination of total drug (1), multiple analytes in combination therapies (2)(3)(4), products of post-translational modifications (5), as well as protein catabolites (6). As biotherapeutics progress from discovery into development, their bioanalytical assays must be validated to meet global regulatory requirements.…”

Absolute and Multiplex Quantification of Antibodies in Serum Using Psaq™ Standards and LC-MS/MS

“…In contrast, LC-MS/MS approaches and targeted MS approaches -which are based on the monitoring of proteotypic peptides -can detect protein isoforms or mAb variants carrying minor amino acid modifications. Since 2008, several industrial pharmaceutical research groups have developed targeted LC-MS approaches for the quantification of biotherapeutics during preclinical and clinical studies [22], and very recently, they have started performing multiplex LC-MS/MS assays [23][24][25]. For example, Furlong et al [12] published an elegant approach combining LC-MS/MS and a 'dual universal peptide', while Xu et al [24] described a multiplex LC-MS/MS approach that could be used to measure two co-administered mAbs using isotopically labeled peptides.…”