Concerted application of LC–MS and ligand binding assays to better understand exposure of a large molecule drug
2018
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
pentamerwith 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
biodistributionrather than an assay artifact.
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