Ultra-Sensitive Intact Monoclonal Antibody Quantification Using a Liquid Handling Platform and a LC/Q-TOF Mass Spectrometer

Traditionally, LC/MS for large molecule drug analysis required an enzymatic digestion to cleave larger proteins into smaller peptides more amenable to mass analysis. The disadvantages to this approach are many and include low throughput, incomplete enzymatic reaction, and surrogate peptide bias due to modifications in the molecules. Modern mass spectrometers have allowed researchers to analyze large molecules at their intact level.

We demonstrate an automated LC/MS workflow to quantify intact mAb drugs in mouse plasma. The workflow uses an Agilent AssayMAP Bravo automated liquid handling platform and an Agilent 6545XT AdvanceBio LC/Q-TOF system. Our results show that this automated LC/MS assay can be used for quantitative analysis of biologic therapeutics with excellent sensitivity and reproducibility.

Presenter: Xi Qiu, PhD (LC-MS Application Scientist, Agilent Technologies, Inc.)

Xi Qiu is application scientist at Agilent, he earned his Ph.D. degree from the department of Pharmacognosy and Medicinal Chemistry at University of Illinois at Chicago. Prior to joining Agilent, he worked at Johnson and Johnson where he focused on large molecule quantification using LC-MS at intact and peptide level as well as contract research organizations leading large molecule LC-MS group performing protein, protein conjugates, peptide, and oligos analysis.