Sensitive liquid chromatographic assay for the simultaneous determination of 5-fluorouracil and its prodrug, tegafur, in beagle dog plasma

Chu, Dafeng; Gu, Jingkai; Liu, Wanhui; Fawcett, J. Paul; Dong, Qinghai

doi:10.1016/s1570-0232(03)00571-3

Cited by 40 publications

(30 citation statements)

References 8 publications

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“…High-performance liquid chromatography (HPLC) is the method of choice for this purpose. The present study first confirmed simultaneous determination of FT and 5-FU levels in low-volume serum samples after oral administration of TS-1 by applying the HPLC method developed by Chu et al (2003). 1) Chemotherapy with TS-1 has been widely employed in the treatment of oral cancer.…”

Section: Introductionsupporting

confidence: 66%

“…The present study first confirmed simultaneous determination of FT and 5-FU levels in low-volume serum samples after oral administration of TS-1 by applying the HPLC method developed by Chu et al (2003). 1) Chemotherapy with TS-1 has been widely employed in the treatment of oral cancer. In cases where oral cancer patients suffer from dysphagia (or other swallowing disorders), TS-1 may have to be tube-administered by opening capsules instead of oral administration.…”

Section: Introductionsupporting

confidence: 66%

“…Determination of Serum Concentrations of FT and 5-FU --The HPLC assay method reported by Chu et al (2003) for 500 µl of dog samples was applied to half volumes of human samples.…”

Section: Methodsmentioning

confidence: 99%

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Feasibility of Bioavailability Testing by Simultaneous Determination of Serum Concentrations of Tegafur and 5-fluorouracil after TS-1 Oral or Tube Administration for Chemotherapy in Oral Cancer Patients

Nakamoto

Ishigouoka

Sato³

et al. 2010

JOURNAL OF HEALTH SCIENCE

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TS-1 is an oral anticancer agent comprising three components: two biochemical modulators of 5-fluorouracil (5-FU) and tegafur (FT), a prodrug of 5-FU. TS-1 displays potent anti-tumor activity by maintaining effective 5-FU concentrations in serum for a prolonged period. FT is gradually converted to 5-FU in vivo via 5'-hydroxylation mediated by cytochrome P450s. As a result, genetic polymorphisms can cause wide individual differences in serum concentration of 5-FU after administration of TS-1, requiring monitoring of serum concentration of 5-FU for each patient. Chemotherapy with TS-1 plays a major role in the treatment of oral cancer. In cases where a patient with oral cancer shows dysphagia, TS-1 may need to be tube-administered. Although tube administration by the simple suspension method has been recommended from a biosafety perspective, particularly for anti-cancer agents, its efficacy remains unclear. We established a simple high-performance liquid chromatography method for simultaneous determination of FT and 5-FU levels at clinical sites by modifying a method reported in the literature.1) Unlike the original method, this simplified method does not require extraction procedures to separate FT and 5-FU, and requires only 250 µl of serum. Using this method, we compared FT concentrations in the sera of oral cancer patients administered TS-1 orally or via a tube-assisted simple suspension method. No significant differences in FT concentrations were apparent between these two modes of administration. TS-1 treatment by tube administration using the simple suspension method thus seems useful for patients with dysphagia as an alternative to oral dosage.

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Section: Introductionsupporting

confidence: 66%

Section: Introductionsupporting

confidence: 66%

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Feasibility of Bioavailability Testing by Simultaneous Determination of Serum Concentrations of Tegafur and 5-fluorouracil after TS-1 Oral or Tube Administration for Chemotherapy in Oral Cancer Patients

Nakamoto

Ishigouoka

Sato³

et al. 2010

JOURNAL OF HEALTH SCIENCE

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“…Plasma samples consisting of FT and CDHP, which have different chemical and physical properties, were all to be pretreated by liquid-liquid extraction using dichloromethane, isopropanol:ethyl acetate (15:85, v/v) and n-propanol:ether (16:84, v/v) as an extraction agent. [9][10][11][12][13][14]16,18,20 However, protein precipitation was used for sample preparation after comparing the liquid-liquid extraction, and methanol was chosen as a precipitation agent in this study. Protein precipitation is more advisable and advantageous in the present work of FT and CDHP, because it could not only ensure a good cleanup of the plasma samples, adequate recoveries and high sensitivity, but also be performed simply.…”

Section: Sample Preparationmentioning

confidence: 99%

“…On the other hand, HPLC or LC/MS/MS methods for the quantification of FT alone in plasma samples have also been reported. [17][18][19][20] These methods require a time-consuming extraction procedure, and a 20 -30 min runtime. There was a paper about the HPLC method for the determination of CDHP alone for an in vitro sample, 6 but this method is not suitable for detailed pharmacokinetic studies in humans, because of poor specificity or inadequate sensitivity.…”

mentioning

confidence: 99%

Simultaneous Determination of Tegafur and Gimeracil in Human Plasma by Liquid Chromatography/Tandem Mass Spectrometry

Lü

et al. 2009

ANAL. SCI.

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We developed a rapid, simple and sensitive LC/MS/MS method for the simultaneous quantitation of tegafur (FT) and gimeracil (CDHP) in human plasma with a concentration range of 20 -5000 and 2 -500 ng/mL, respectively. Methanol was chosen as a precipitation agent for sample preparation. Chromatographic separation was performed on an inertsil ODS-3 C18 column using 1.0% formic acid in water and methanol (80/20, v/v) at a flow rate of 0.3 mL/min. The MS detection was operated with selected reaction monitoring (SRM) in the positive-ion mode. The matrix effect ranged from -8.9 to 7.8% for all analytes. The intra-and inter-day precisions were less than 8.6 and 9.5%, and the accuracy was within ±7.5% for all analytes, respectively. The mean recoveries were 76.5 ± 5.2 and 78.3 ± 5.9% for FT and CDHP, respectively. The analytes were stable under all possible conditions of storing and handling for each compound.

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Synthesis and Characterization of New Liver Targeting 5‐Fluorouracil‐Cholic Acid Conjugates

Qian

et al. 2009

Archiv der Pharmazie

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The objective of this work was to develop a liver-specific antihepato carcinoma agent. A series of 5-fluorouracil / cholic acid conjugates (5-FU-cholic acid conjugates) were prepared and tested for their chemical characteristics and bio-distribution properties. The in-vitro stability trial showed 5-FU-cholic acid conjugates could be completely hydrolyzed by heating at 70 degrees C in an acidic solution, pH = 1, for 5 min. The fast and complete hydrolysis of these compounds could be compatible with a fast separation and analysis method to shorten the analysis time. The decomposition speeds of the 5-FU-cholic acid conjugates in different organs of mice at several time points after oral administration were evaluated by measuring the concentrations of regenerated 5-FU in organ tissue. The results were compared with those of the controls, which was a group of mice orally taking 5-FU. The concentrations of 5-FU in mice liver tissue were remarkably increased after oral administration of the prodrugs, and were much larger than if only orally administered 5-FU. The results suggested the feasibility to improve therapeutic efficiency of liver targeting treatments by using cholic acid as the vector of drugs.

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Sensitive liquid chromatographic assay for the simultaneous determination of 5-fluorouracil and its prodrug, tegafur, in beagle dog plasma

Cited by 40 publications

References 8 publications

Feasibility of Bioavailability Testing by Simultaneous Determination of Serum Concentrations of Tegafur and 5-fluorouracil after TS-1 Oral or Tube Administration for Chemotherapy in Oral Cancer Patients

Feasibility of Bioavailability Testing by Simultaneous Determination of Serum Concentrations of Tegafur and 5-fluorouracil after TS-1 Oral or Tube Administration for Chemotherapy in Oral Cancer Patients

Simultaneous Determination of Tegafur and Gimeracil in Human Plasma by Liquid Chromatography/Tandem Mass Spectrometry

Synthesis and Characterization of New Liver Targeting 5‐Fluorouracil‐Cholic Acid Conjugates

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