Method development and validation of LC-MS/MS-based assay for the simultaneous quantitation of trastuzumab and pertuzumab in cynomolgus monkey serum and its application in pharmacokinetic study.
LC-MS/MS
antibody cocktail
method validation
pharmacokinetic
quantitative analysis
Journal
Biomedical chromatography : BMC
ISSN: 1099-0801
Titre abrégé: Biomed Chromatogr
Pays: England
ID NLM: 8610241
Informations de publication
Date de publication:
Dec 2020
Dec 2020
Historique:
received:
05
04
2020
revised:
12
05
2020
accepted:
15
05
2020
pubmed:
20
5
2020
medline:
20
4
2021
entrez:
20
5
2020
Statut:
ppublish
Résumé
We present a simple and robust LC-MS/MS assay for the simultaneous quantitation of an antibody cocktail of trastuzumab and pertuzumab in monkey serum. The LC-MS/MS method saved costs, decreased the analysis time, and reduced quantitative times relative to the traditional ligand-binding assays. The serum samples were digested with trypsin at 50°C for 60 min after methanol precipitation, ammonium bicarbonate denaturation, dithiothreitol reduction, and iodoacetamide alkylation. The tryptic peptides were chromatographically separated using a C18 column (2.1 × 50 mm, 2.6 μm) with mobile phases of 0.1% formic acid in water and acetonitrile. The other monoclonal antibody, infliximab, was used as internal standards to minimize the variability during sample processing and detection. A unique peptide for each monoclonal antibody was simultaneously quantified using LC-MS/MS in the multiple reaction monitoring mode. Calibration curves were linear from 2.0 to 400 μg/mL. The intra- and inter-assay precision (%CV) was within 8.9 and 7.4% (except 10.4 and 15.1% for lower limit of quantitation), respectively, and the accuracy (%Dev) was within ±13.1%. The other validation parameters were evaluated, and all results met the acceptance criteria of the international guiding principles. Finally, the method was successfully applied to a pharmacokinetics study after a single-dose intravenous drip administration to cynomolgus monkeys.
Substances chimiques
Antibodies, Monoclonal, Humanized
0
pertuzumab
K16AIQ8CTM
Trastuzumab
P188ANX8CK
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e4903Subventions
Organisme : National Major Scientific and Technological Special Project for "Significant New Drugs Development"
ID : 2020ZX09201026
Informations de copyright
© 2020 John Wiley & Sons, Ltd.
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