Comprehensive performance evaluation of ligand-binding assay-LC-MS/MS method for co-dosed monoclonal anti-SARS-CoV-2 antibodies (AZD7442).
Bioanalysis
; 16(7): 149-163, 2024 Apr.
Article
en En
| MEDLINE
| ID: mdl-38385904
ABSTRACT
Aims:
AZD7442 is a combination SARS-CoV-2 therapy comprising two co-dosed monoclonal antibodies. Materials &methods:
The authors validated a hybrid ligand-binding assay-LC-MS/MS method for pharmacokinetic assessment of AZD7442 in human serum with nominal concentration range of each analyte of 0.300-30.0 µg/ml.Results:
Validation results met current regulatory acceptance criteria. The validated method supported three clinical trials that spanned more than 17 months and ≥720 analytical runs (â¼30,000 samples and â¼3000 incurred sample reanalyses per analyte). The data generated supported multiple health authority interactions, across the globe. AZD7442 (EVUSHELD) was approved in 12 countries for pre-exposure prophylaxis of COVID-19.Conclusion:
The results reported here demonstrate the robust, high-throughput capability of the hybrid ligand-binding assay-LC-MS/MS approach being employed to support-next generation versions of EVUSHELD, AZD3152.
The measurement of antibodies in human body fluids (e.g., blood, serum) has historically been tied to laboratory tests that may face operational limitations, including susceptibility to interference from other blood components and a reliance on unique reagents that can take months to produce. As such, there is a pursuit of alternative analytical methods to more accurately detect and measure antibody drugs from complex matrices. In the method, the authors describe different techniques that once combined were used to capture, separate, filter, fragment and then detect and measure the co-dosed antibody drugs. This method has been validated in accordance with current health authority guidelines and has been used to support three clinical trials that spanned more than 17 months; that is, the validated method was used to analyze nearly 30,000 serum samples from more than 2000 patients. Collectively, the results reported here demonstrate the robustness and high-throughput capability of this analytical approach.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Anticuerpos Neutralizantes
/
COVID-19
/
Cromatografía Líquida con Espectrometría de Masas
Límite:
Humans
Idioma:
En
Revista:
Bioanalysis
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos