Simultaneous determination of nine tyrosine kinase inhibitors by 96-well solid-phase extraction and ultra performance LC/MS-MS.
Clin Chim Acta
; 412(11-12): 1060-7, 2011 May 12.
Article
en En
| MEDLINE
| ID: mdl-21345336
ABSTRACT
BACKGROUND:
Tyrosine Kinase Inhibitors (TKIs) are a class of targeted drugs for the treatment of malignant pathologies. The metabolic profile of these drugs can result in great interindividual variability, thus therapeutic drug monitoring (TDM) is of importance. Here, a rapid and specific method for quantification of nine TKIs in plasma samples is described.METHODS:
Chromatography was performed on a Waters Acquity-UPLC® system with BEH C18-50*2.1 mm column, under a gradient of ammonium formate-acetonitrile. An Acquity-TQD® with electrospray ionization was used for detection. Samples were prepared by solid phase extraction (Oasis® MCX µElution) and eluate was injected in the system.RESULTS:
Calibration curves ranged from 10 to 5000 ng/mL for imatinib, its metabolite, nilotinib, lapatinib, erlotinib and sorafenib and from 0.1 to 200 ng/mL for dasatinib, axitinib, gefitinib and sunitinib. Peaks of each compound (retention time from 0.76 to 2.51 min) were adequately separated. The mean relative extraction recovery was in the range of 90.3-106.5% thanks to the use of stable isotopes as internal standard. There was no significant ion suppression observed at the respective TKI retention times.CONCLUSION:
This rapid, sensitive and specific UPLC/MS-MS method is able to perform simultaneous quantification of nine TKIs in human plasma and usable for routine TDM.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Análisis Químico de la Sangre
/
Proteínas Tirosina Quinasas
/
Cromatografía Líquida de Alta Presión
/
Inhibidores de Proteínas Quinasas
/
Espectrometría de Masas en Tándem
/
Extracción en Fase Sólida
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Clin Chim Acta
Año:
2011
Tipo del documento:
Article
País de afiliación:
Francia