Title:The Development of a Rapid, Simple and Sensitive LC-MS/MS Method, to Guide Clinical Dosing, for the Analysis of 5-Fluorouracil in Human Plasma
Volume: 13
Issue: 4
Author(s): Wenxuan He*, Jennifer H Martin, P Nicholas Shaw, Euan T Walpole and Goce Dimeski
Affiliation:
- Department of Chemistry and Chemical Engineering, The University of Minjiang, Fuzhou, P.R.,China
Keywords:
5-Fluorouracil, LC-MS/MS, human plasma, protein precipitation, antineoplastic drug, sample preparation technique.
Abstract: Introduction: 5-Fluorouracil is a commonly prescribed antineoplastic drug. Historically, methods
to determine this compound in biological fluids have been time consuming or not sensitive enough.
Materials and Methods: In this report, a method using simple and rapid sample preparation with good
sensitivity, precision and accuracy for the quantitative determination of 5-fluorouracil in human plasma
by LC-MS/MS is established and validated. By the judicious combination of a small amount of injected
sample, low flow rate, careful control of gradient elution profile, use of a HILIC pre-column to further
remove residual phospholipids and an isotopically labelled internal standard (ILIS), the method has
successfully overcome matrix effect with protein precipitation sample pre-treatment without evaporating
to dryness and reconstituting process.
Conclusion: This newly developed method can be used to measure patient plasma concentrations of 5-
fluorouracil, as low as 0.8 ng/mL and as high as 100 µ g/mL, with less than 15% both intra- and interday
accuracy and precision. Such a methodology will be very convenient of being used in routine therapeutic
drug monitoring.
