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

Author(s): Wenxuan He*, Jennifer H Martin, P Nicholas Shaw, Euan T Walpole, Goce Dimeski.

Journal Name: Current Pharmaceutical Analysis

Volume 13 , Issue 4 , 2017

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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.

Keywords: 5-Fluorouracil, LC-MS/MS, human plasma, protein precipitation, antineoplastic drug, sample preparation technique.

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Article Details

VOLUME: 13
ISSUE: 4
Year: 2017
Page: [378 - 383]
Pages: 6
DOI: 10.2174/1573412912666160811114339
Price: $58

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