Application of an electrochemiluminescence assay for quantification of E6011, an antifractalkine monoclonal antibody, to pharmacokinetic studies in monkeys and humans.
E6011
electrochemiluminescence
humans
monkey
validation
Journal
Journal of clinical laboratory analysis
ISSN: 1098-2825
Titre abrégé: J Clin Lab Anal
Pays: United States
ID NLM: 8801384
Informations de publication
Date de publication:
Jan 2019
Jan 2019
Historique:
received:
21
05
2018
accepted:
30
06
2018
pubmed:
22
7
2018
medline:
16
2
2019
entrez:
22
7
2018
Statut:
ppublish
Résumé
E6011, a humanized antifractalkine monoclonal antibody, is under development for the treatment of various inflammatory diseases, such as rheumatoid arthritis. A reproducible assay method has been developed for the determination of E6011 in monkey and human serum by electrochemiluminescence (ECL) assay. E6011 in serum was captured by fractalkine and detected by ruthenium-labeled rabbit anti-E6011 Fab polyclonal antibodies for ECL detection. E6011 in serum was quantifiable from 0.02 and 0.1 μg/mL in monkey and human serum, respectively, with minimum required dilution of 500. The method was then validated in accordance with bioanalytical guidelines. Accuracy and precision of quality control samples at five concentrations in intra- and interbatch reproducibility demonstrated that relative error and relative standard deviation were within acceptable criteria. Recovery of E6011 was 92.9%-121.7% and 85.0%-109.3% in humans and monkeys. Dilution integrity, no prozone effects, and no impacts by antigen were also ensured. Parallelism was also confirmed using incurred clinical sample analysis. Various types of stability were assessed, which confirmed that E6011 in serum was stable for 367 and 735 days in monkey and human sera, respectively, under frozen conditions. The developed method was successfully applied supporting pharmacokinetic studies in monkeys and humans.
Sections du résumé
BACKGROUND
BACKGROUND
E6011, a humanized antifractalkine monoclonal antibody, is under development for the treatment of various inflammatory diseases, such as rheumatoid arthritis. A reproducible assay method has been developed for the determination of E6011 in monkey and human serum by electrochemiluminescence (ECL) assay.
METHODS
METHODS
E6011 in serum was captured by fractalkine and detected by ruthenium-labeled rabbit anti-E6011 Fab polyclonal antibodies for ECL detection. E6011 in serum was quantifiable from 0.02 and 0.1 μg/mL in monkey and human serum, respectively, with minimum required dilution of 500. The method was then validated in accordance with bioanalytical guidelines.
RESULTS
RESULTS
Accuracy and precision of quality control samples at five concentrations in intra- and interbatch reproducibility demonstrated that relative error and relative standard deviation were within acceptable criteria. Recovery of E6011 was 92.9%-121.7% and 85.0%-109.3% in humans and monkeys. Dilution integrity, no prozone effects, and no impacts by antigen were also ensured. Parallelism was also confirmed using incurred clinical sample analysis. Various types of stability were assessed, which confirmed that E6011 in serum was stable for 367 and 735 days in monkey and human sera, respectively, under frozen conditions.
CONCLUSION
CONCLUSIONS
The developed method was successfully applied supporting pharmacokinetic studies in monkeys and humans.
Identifiants
pubmed: 30030862
doi: 10.1002/jcla.22625
pmc: PMC6430341
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Monoclonal, Humanized
0
quetmolimab
G8NT4Q571B
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e22625Informations de copyright
© 2018 Wiley Periodicals, Inc.
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J Clin Lab Anal. 2019 Jan;33(1):e22625
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