Determination and quantification of intracellular fludarabine triphosphate, cladribine triphosphate and clofarabine triphosphate by LC-MS/MS in human cancer cells.
J Chromatogr B Analyt Technol Biomed Life Sci
; 1053: 101-110, 2017 May 15.
Article
en En
| MEDLINE
| ID: mdl-28415014
ABSTRACT
Purine nucleoside analogues are widely used in the treatment of haematological malignancies, and their biological activity is dependent on the intracellular accumulation of their triphosphorylated metabolites. In this context, we developed and validated a liquid chromatography tandem mass spectrometry (LC-MS/MS) method to study the formation of 5'-triphosphorylated derivatives of cladribine, fludarabine, clofarabine and 2'-deoxyadenosine in human cancer cells. Br-ATP was used as internal standard. Separation was achieved on a hypercarb column. Analytes were eluted with a mixture of hexylamine (5 mM), DEA (0.4%, v/v, pH 10.5) and acetonitrile, in a gradient mode at a flow rate of 0.3mLmin-1. Multiple reactions monitoring (MRM) and electrospray ionization in negative mode (ESI-) were used for detection. The application of this method to the quantification of these phosphorylated cytotoxic compounds in a human follicular lymphoma cell line, showed that it was suitable for the study of relevant biological samples.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Polifosfatos
/
Vidarabina
/
Arabinonucleósidos
/
Nucleótidos de Adenina
/
Cladribina
/
Espectrometría de Masas en Tándem
/
Antineoplásicos
Límite:
Humans
Idioma:
En
Revista:
J Chromatogr B Analyt Technol Biomed Life Sci
Asunto de la revista:
ENGENHARIA BIOMEDICA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Francia
Pais de publicación:
HOLANDA
/
HOLLAND
/
NETHERLANDS
/
NL
/
PAISES BAJOS
/
THE NETHERLANDS