Concerted application of LC-MS and ligand binding assays to better understand exposure of a large molecule drug.
Bioanalysis
; 10(16): 1261-1272, 2018 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-29923414
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.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Bioensaio
/
Preparações Farmacêuticas
/
Espectrometria de Massas em Tandem
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article