Concerted application of LC–MS and ligand binding assays to better understand exposure of a large molecule drug. (20th June 2018)

• Record Type: Journal Article
• Authors: Xu, Weifeng; Jiang, Hao; Titsch, Craig; Gadkari, Snaehal; Batog, Alicja; Wang, Bonnie; Hippeli, Lauren; Yamamoto, Brent; Chadwick, Kristina; Wheeler, Jennifer; Thompson, Chris; Stahl, James; Willett, Scott; DeSilva, Binodh S; Myler, Heather; Dodge, Robert W; Pillutla, Renuka C
• Is Part Of: Bioanalysis. Volume 10:Number 16(2018)
• Page Start: 1261
• Page End: 1272
• Publication Date: 2018-06-20
• Subjects: bioanalysis -- biodistribution -- biotherapeutic -- LC–MS -- ligand binding assay -- pharmacokinetics; Drugs -- Analysis -- Periodicals; 615.19005
• DOI: 10.4155/bio-2018-0108
• Languages: English
• ISSNs: 1757-6180

Abstract

Aim: A ligand-binding assay (LBA) was used to measure exposure of PRM-151, the recombinant form of human pentraxin-2 (PTX-2), a complex pentamer with multiple binding partners. However, the assay showed a lack of dose-dependent exposure in select preclinical species and it could not differentiate the infused PRM-151 from the endogenous PTX-2 in nonhuman primates.Materials & methods: Instead of assessing interference from its multiple binding partners, which could be time consuming and laborious, a LC–MS assay avoid of these interference was implemented to measure 'total' drug without the use of immunoaffinity capture reagents.Results & Conclusion: The resultant LC–MS data confirmed the original data and the lack of dose-dependent exposure is now understood to be due to the multiple and diverse targets and functions and resultant complex biodistribution rather than an assay artifact.