Measurement of methotrexate polyglutamates in human erythrocytes by ion-pair UPLC-MS/MS.
Published
Journal Article
BACKGROUND: Low-dose methotrexate is used for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis, but its effectiveness greatly varies between individuals. Therapeutic drug monitoring of intracellular methotrexate metabolites, the γ-polyglutamates (MTXGlu(n)), in human erythrocytes has shown promise in providing a basis for individualization of therapy. RESULTS: This work presents expedient methodology for the analysis of MTXGlu(1-7) in human erythrocytes by ion-pair UPLC with detection by tandem MS (UPLC-ESI-MS/MS). The use of N,N-dimethylheptylamine as an ion-pair agent was found to be favorable over others. Thermal extraction of erythrocyte lysates provides a simple one-step extraction procedure. The entire chromatographic run time is 6 min and the assay was validated within the therapeutic range of these metabolites CONCLUSION: The developed sample preparation procedure in combination with ion-pair UPLC-ESI-MS/MS analysis allowed for expedient quantitation of MTXGlu(1-7) in human erythrocytes. The rapid analysis time would enable therapeutic drug monitoring of MTXGlu(1-7) in the clinic.
Full Text
Duke Authors
Cited Authors
- van Haandel, L; Becker, ML; Williams, TD; Leeder, JS; Stobaugh, JF
Published Date
- December 2011
Published In
Volume / Issue
- 3 / 24
Start / End Page
- 2783 - 2796
PubMed ID
- 22185278
Pubmed Central ID
- 22185278
Electronic International Standard Serial Number (EISSN)
- 1757-6199
Digital Object Identifier (DOI)
- 10.4155/bio.11.288
Language
- eng
Conference Location
- England