Comprehensive workflow for Automated Sample Cleanup and Sensitive Quantitation of Glucagon-like peptide-1 (GLP-1) Analogs from Plasma

In recent years, glucagon-like peptide-1 receptor (GLP-1R) agonists have gained significant attention because of their effectiveness to treat obesity and type 2 diabetes. The global market for GLP-1 analogues is projected to grow rapidly, reaching $260 billion by 2034. Developing sensitive bioanalytical assays to determine pharmacokinetics and toxicokinetics is crucial for advancing these medications. 

Traditionally, the plasma concentration of GLP-1 analogs was measured by ligand binding assay, which requires time to develop antibody and lack selectivity and specificity. Liquid chromatography-mass spectrometry (LC/MS), which is used for sequence identification of GLP-1 receptor agonists, has emerged as an alternative methodology to precise quantify these molecules in biological matrix because of its superior sensitivity, wide dynamic range, and high specificity. Here we present an automated workflow, which combines automation and LC/MS technologies, to quantify GLP-1 analog drug in human plasma by using an Agilent 1290 Infinity II Bio LC and an Agilent 6495D triple quadrupole system (Figure 1). Our results indicate that this automated LC/MS workflow can enhance assay sensitivity by five times compared to traditional organic solvent precipitation. 

This workflow can be used for quantitative analysis of GLP-1 therapeutics without the need to have specific antibody while providing excellent sensitivity, high specificity and fast method development, which will play a crucial role in drug discovery and development.

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

Xi Qiu is application scientist at Agilent, he has extensive experience using LC-MS for large molecules analysis including protein, protein conjugates, peptide, and oligos. He earned his Ph.D. degree from the department of Pharmacognosy and Medicinal Chemistry at University of Illinois at Chicago focusing on benefits and safety of botanical dietary supplements and herbal-drug interactions. After graduation, he did his postdoc training at Pfizer and Bristol Myers Squibb where he worked on drug transporters protein expression analysis in tissues as well as drug induced liver injury mechanism. He then worked for two major contract research organizations leading their large molecule LC-MS group performing protein, protein conjugates, peptide, and oligos pharmacokinetics/toxicokinetics analysis under GLP/regulated environment. 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.