A stability indicating LC-MS/MS method for quantification of a NOX Inhibitor R14 in its bisulfite adduct form for pharmacokinetic studies.
J Pharm Biomed Anal
; 228: 115326, 2023 May 10.
Article
en En
| MEDLINE
| ID: mdl-36924633
ABSTRACT
R14, also known as NOX Inhibitor VII, is a potent inhibitor of NADPH oxidases (NOX) which has recently been identified as a novel agent targeting to triple-negative breast cancer. It is also rapidly degraded in collected pharmacokinetic plasma and blood samples even stored under - 70 °C. The purpose of this study was to develop a stability indicating LC-MS/MS assay that would be suitable for quantification of R14 in plasma and blood. In the presence of sodium sulfite under acidic pH, R14, an aryl lactam compound which is not a typically reactive compound for bisulfite addition, readily and completely converted to R14 bisulfite adduct, which was more stable in plasma and blood. The adduct has MRM transition at m/z 340.1-127.0 in negative mode and showed high sensitivity in LC-MS/MS quantification. Thus, monitoring the adduct provided a suitable way of quantitating R14 concentrations in mouse whole blood. The reacting conditions were optimized based on detecting R14 bisulfite adduct, and the assay was established and validated on a SCIEX 6500+ Triple Quad LC-MS/MS System. The method was then successfully adapted to pharmacokinetic studies after oral administration of R14 to mice.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Espectrometría de Masas en Tándem
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Pharm Biomed Anal
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos