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Pharmacokinetic application of a bio‐analytical LC‐MS method developed for 5‐fluorouracil and methotrexate in mouse plasma, brain and urine
Author(s) -
Ganti Vaishnavi,
Walker Ellen A.,
Nagar Swati
Publication year - 2013
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.2893
Subject(s) - chemistry , chromatography , pharmacokinetics , urine , ammonium acetate , methotrexate , quadrupole mass analyzer , detection limit , high performance liquid chromatography , elution , quantitative analysis (chemistry) , mass spectrometry , pharmacology , biochemistry , biology , medicine , immunology
In the past we have reported significant cognitive deficits in mice receiving 5‐fluorouracil in combination with low‐dose methotrexate. To explain such interactions, a pharmacokinetic study was designed. A sensitive bio‐analytical method was therefore developed and validated for 5‐fluorouracil and methotrexate in mouse plasma, brain and urine with liquid chromatography coupled to a single quadrupole mass spectrometer. Chromatographic separation was accomplished by Agilent® Zorbax® SB‐C 18 column, with isocratic elution (5 mM ammonium acetate and methanol, 70:30, %v/v) at a flow rate of 300 μL/min. The limit of quantitation for both drugs was 15.6 ng/mL (plasma and brain) and 78.1 ng/mL (urine), with interday and intraday precision and accuracy ≤15% and a total run time of 6 min. This bio‐analytical method was used for the pharmacokinetic characterization of 5‐fluorouracil and methotrexate in mouse plasma, brain and urine over a period of 24 h. This method allowed characterization of the brain concentrations of 5‐fluorouracil over a period of 24 h. Copyright © 2013 John Wiley & Sons, Ltd.