Document Detail


Validation of a ligand binding assay using dried blood spot sampling.
MedLine Citation:
PMID:  23135927     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Dried blood spots (DBS) technology has been introduced as a microsampling alternative to traditional plasma or serum sampling for pharmacokinetics or toxicokinetics evaluation. The application of DBS has been established for many small molecule drugs at discovery, nonclinical, and clinical stages. However, the application of DBS for large molecule therapeutics development is not yet well-established. This article describes the method validation of a ligand binding assay (LBA) for DBS sampling of a therapeutic monoclonal antibody-AMG 162 (Denosumab). The original serum LBA was modified for the DBS method. A fit-for-purpose method validation was performed to evaluate accuracy and precision, selectivity, dilutional linearity, and stability. In addition, the parameters relevant to DBS, such as spot volume, extraction recovery, whole blood stability, and hematocrit effects, were evaluated. The validation results demonstrated assay robustness with inter-assay precision of ≤ 19%, inter-assay accuracy of ≤ 9%, and total error of ≤ 24%. Selectivity, extraction recovery, dilutional linearity, and stability were demonstrated. The validation results revealed some limitations of the possible effect of blood hematocrit on therapeutic concentration measurements and the caution required using whole blood for standards and quality controls preparation. This is the first article to describe a thorough method validation of an LBA using DBS for a therapeutic monoclonal antibody. The lessons learned can serve as a model process for future method validation of other LBAs for large molecule therapeutics or biomarkers using the DBS sampling method.
Authors:
Daniel Burns; Laura Brunner; Surendran Rajendran; Beth Johnson; Mark Ma; Jin Wang
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Publication Detail:
Type:  Journal Article; Validation Studies     Date:  2012-11-08
Journal Detail:
Title:  The AAPS journal     Volume:  15     ISSN:  1550-7416     ISO Abbreviation:  AAPS J     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-03     Completed Date:  2013-08-02     Revised Date:  2013-11-14    
Medline Journal Info:
Nlm Unique ID:  101223209     Medline TA:  AAPS J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  123-31     Citation Subset:  IM    
Affiliation:
Pharmacokinetics and Drug Metabolism Department, Amgen Inc., Mail Stop 30E-3-C, One Amgen Center Drive, Thousand Oaks, CA 91320, USA.
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MeSH Terms
Descriptor/Qualifier:
Antibodies, Monoclonal, Humanized / metabolism*
Blood Preservation
Dried Blood Spot Testing / methods*
Hematocrit
Humans
Ligands
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal, Humanized; 0/Ligands; 4EQZ6YO2HI/denosumab
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