Flame‐Ionization GLC Assay for Fluorouracil in Plasma of Cancer Patients

Leenheer, A.P. De

doi:10.1002/jps.2600680931

Cited by 10 publications

(2 citation statements)

References 15 publications

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“…Various methods for the determination of 5-FU in biological matrix have been reported. These methods employ gas chromatography, tachophoresis or highperformance liquid chromatography (HPLC) as separating technologies, with radioactivity, nitrogen-phosphorus flame-ionization, ultraviolet, fluorescence or mass spectrometry as detection techniques [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] . Unfortunately, most of these methods required laborious sample preparation involving derivatization step before analysis, long runtime and complex apparatus.…”

Section: -Fluorouracil (5-fumentioning

confidence: 99%

Determination of 5-fluorouracil in human plasma by high-performance liquid chromatography (HPLC)

Lü

et al. 2010

Trans. Tianjin Univ.

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Abstract：5-Fluorouracil (5-FU) has a broad spectrum of anti-tumor activity, widely applied to the treatment of cancers. However, it is necessary to determine the plasma concentration of 5-FU in clinical practice due to its narrow therapeutic index. Therefore, a simple, economic and sensitive high-performance liquid chromatography (HPLC) method was developed and validated for the determination of 5-FU in human plasma. Ethyl acetate was chosen as extraction reagent. Chromatographic separation was performed on a Diamonsil C 18 column (250 mm × 4.6 mm i.d., 5 μm) with the mobile phase consisting of methanol and 20 mmol/L ammonium formate using a linear gradient elution at a flow rate of 0.8 mL/min. 5-FU and 5-bromouracil (5-BU) were detected by UV detector at 265 nm. The calibration curve was linear over the concentration range of 5-500 ng/mL and the correlation coefficient was not less than 0.992 6 for all calibration curves. The intra-and inter-day precisions were less than 10.5% and 4.3%, respectively, and the accuracy was within ±3.7%. The recovery at all concentration levels was 80.1±8.6%. 5-FU was stable under possible conditions of storing and handling. This method is proved applicable to therapeutic drug monitoring and pharmacokinetic studies of 5-FU in human. Keywords：5-fluorouracil(5-FU); high-performance liquid chromatography (HPLC); human plasma 5-Fluorouracil (5-FU, Fig.1) is still a mainstay in the treatment of various cancers including head and neck cancer, gastrointestinal tract cancer and breast cancer since being introduced into practice in the 1950s [1] . In addition, several prodrugs of 5-FU, such as capecitabine and tegafur, were developed. The action mechanism of 5-FU is that 5-FU is converted into 5-fluoro-20-deoxyuridine monophosphate, and then irreversibly inhibits activity of thymidylate synthase to result in decreased intracellular concentrations of deoxythymidine monophosphate and DNA damage [2] . However, 5-FU, as activated metabolite of many derivatives and novel formulations, has the disadvantage of a low and unpredictable bioavailability (between 28% and 100%) [3] . Thus, 5-FU plasma concentrations have been correlated with toxicity and efficacy. Furthermore, therapeutic drug monitoring has been reported to result in an improved response/toxicity balance, and hence pharmacokinetic studies of 5-FU in human are more important and necessary. (a) 5-FU (b) 5-Bromouracil

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Section: -Fluorouracil (5-fumentioning

confidence: 99%

Determination of 5-fluorouracil in human plasma by high-performance liquid chromatography (HPLC)

Lü

et al. 2010

Trans. Tianjin Univ.

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“…Numerous methods for the quantitation of 5‐FU have been reported. They have used thin layer chromatography, gas chromatography, tachophoresis, or high‐performance liquid chromatography (HPLC) as separating modalities, and radioactivity, flame ionization, fluorescence, ultraviolet absorption, or mass spectrometry as detection techniques 8–29. Many of these assays have proven useful and have been applied in pre‐clinical and clinical pharmacological studies.…”

mentioning

confidence: 99%

Quantitation of 5‐fluorouracil (5‐FU) in human plasma by liquid chromatography/electrospray ionization tandem mass spectrometry

Kosovec

Egorin

Gjurich

et al. 2007

Rapid Comm Mass Spectrometry

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5-Fluorouracil (5-FU) has long had a place in the treatment of many malignancies. 5-FU plasma concentrations have been correlated with toxicity and efficacy, and therapeutic drug monitoring has been reported to result in an improved response/toxicity balance. We report validation, according to FDA guidelines, of a hydrophilic interaction chromatography (HILIC) liquid chromatography/tandem mass spectrometry (LC/MS/MS) assay for the sensitive, accurate and precise quantitation of 5-FU in human plasma. The assay employed an isotopically labeled 5-FU internal standard and ethyl acetate extraction. Separation was achieved with an amino column and an isocratic mobile phase of 0.1% formic acid in acetonitrile/water (97:3, v/v), followed by a wash. Detection consisted of electrospray, negative-mode ionization tandem mass spectrometry in the multiple reaction monitoring (MRM) mode. The accuracy was 96.0-102.2%, and precision was 2.1-7.5% in the concentration range of 10-10 000 ng/mL. Recovery from plasma was 46.0-72.6%, and ion suppression was 9.8-25.7%. Plasma freeze/thaw stability was 87.5-104.3%, and stability for 4 h at room temperature was 98.7-100.0%. This assay is currently being used to quantitate 5-FU in human plasma samples.

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Simultaneous Determination of Tegafur and 5-Fluorouracil in Serum by GLC Using Nitrogen-Sensitive Detection

Sugiyama¹,

Kuwamura²,

Odaka³

et al. 1983

Journal of Pharmaceutical Sciences

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Flame‐Ionization GLC Assay for Fluorouracil in Plasma of Cancer Patients

Cited by 10 publications

References 15 publications

Determination of 5-fluorouracil in human plasma by high-performance liquid chromatography (HPLC)

Determination of 5-fluorouracil in human plasma by high-performance liquid chromatography (HPLC)

Quantitation of 5‐fluorouracil (5‐FU) in human plasma by liquid chromatography/electrospray ionization tandem mass spectrometry

Simultaneous Determination of Tegafur and 5-Fluorouracil in Serum by GLC Using Nitrogen-Sensitive Detection

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