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

Kosovec, Juliann E.; Egorin, Merrill J.; Gjurich, Susanna; Beumer, Jan H.

doi:10.1002/rcm.3362

Cited by 57 publications

(41 citation statements)

References 33 publications

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“…Although 5-FU was shown to have substantial antibacterial effects, the tested concentrations in these studies were much higher than what is usually present in vivo. Notwithstanding the fact that after an intravenous bolus injection with 5-FU, plasma concentrations in cancer patients can reach some hundred micromolars, the plasma levels eventually drop to 15-30 µM after 30 min and to 0 µM after 2 h (Casale et al, 2004;Kosovec et al, 2008), owing to the short half-life time (6-22 min) of 5-FU (Bocci et al, 2000). In the case of continuous infusion with 5-FU, the plasma concentrations are much lower, ranging from 3 to 10 µM and kept for a longer time period (24 h) (Joulia et al, 1999;Takimoto et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

5-Fluorouracil sensitivity varies among oral micro-organisms

Vanlancker

Vanhoecke

Smet

et al. 2016

Journal of Medical Microbiology

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5-Fluorouracil (5-FU), a commonly used chemotherapeutic agent, often causes oral mucositis, an inflammation and ulceration of the oral mucosa. Micro-organisms in the oral cavity are thought to play an important role in the aggravation and severity of mucositis, but the mechanisms behind this remain unclear. Although 5-FU has been shown to elicit antibacterial effects at high concentrations (>100 µM), its antibacterial effect at physiologically relevant concentrations in the oral cavity is unknown. This study reports the effect of different concentrations of 5-FU (range 0.1-50 µM) on the growth and viability of bacterial monocultures that are present in the oral cavity and the possible role in the activity of dihydropyrimidine dehydrogenase (DPD), an enzyme involved in 5-FU resistance. Our data showed a differential sensitivity among the tested oral species towards physiological concentrations of 5-FU. Klebsiella oxytoca, Streptococcus salivarius, Streptococcus mitis, Streptococcus oralis, Pseudomonas aeruginosa and Lactobacillus salivarius appeared to be highly resistant to all tested concentrations. In contrast, Lactobacillus oris, Lactobacillus plantarum, Streptococcus pyogenes, Fusobacterium nucleatum and Neisseria mucosa showed a significant reduction in growth and viability starting from very low concentrations (0.2-3.1 µM). We can also provide evidence that DPD is not involved in the 5-FU resistance of the selected species. The observed variability in response to physiological 5-FU concentrations may explain why certain microbiota lead to a community dysbiosis and/or an overgrowth of certain resistant micro-organisms in the oral cavity following cancer treatment.

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Section: Introductionmentioning

confidence: 99%

5-Fluorouracil sensitivity varies among oral micro-organisms

Vanlancker

Vanhoecke

Smet

et al. 2016

Journal of Medical Microbiology

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“…After treatment, the tumors were snap frozen, using liquid nitrogen, and stored at −80°C before drug extraction and quantification. Drug quantification by liquid chromatography (LC)-MS and inductively coupled plasma (ICP)-MS followed previously published methods (30)(31)(32).…”

Section: Methodsmentioning

confidence: 99%

Iontophoretic device delivery for the localized treatment of pancreatic ductal adenocarcinoma

Byrne

Jajja

Schorzman

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Poor delivery and systemic toxicity of many cytotoxic agents, such as the recent promising combination chemotherapy regimen of folinic acid (leucovorin), fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX), restrict their full utility in the treatment of pancreatic cancer. Local delivery of chemotherapies has become possible using iontophoretic devices that are implanted directly onto pancreatic tumors. We have fabricated implantable iontophoretic devices and tested the local iontophoretic delivery of FOLFIRINOX for the treatment of pancreatic cancer in an orthotopic patientderived xenograft model. Iontophoretic delivery of FOLFIRINOX was found to increase tumor exposure by almost an order of magnitude compared with i.v. delivery with substantially lower plasma concentrations. Mice treated for 7 wk with device FOLFIRINOX experienced significantly greater tumor growth inhibition compared with i.v. FOLFIRINOX. A marker of cell proliferation, K i -67, was stained, showing a significant reduction in tumor cell proliferation. These data capitalize on the unique ability of an implantable iontophoretic device to deliver much higher concentrations of drug to the tumor compared with i.v. delivery. Local iontophoretic delivery of cytotoxic agents should be considered for the treatment of patients with unresectable nonmetastatic disease and for patients with the need for palliation of local symptoms, and may be considered as a neoadjuvant approach to improve resection rates and outcome in patients with localized and locally advanced pancreatic cancer.iontophoresis | FOLFIRINOX | pancreatic cancer | device delivery | chemotherapy

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“…64 94,95 or the use of normal phase chromatographic supports. [96][97][98][99] However, all of these approaches suffer from obvious limitations, including long column equilibration, poor kinetic performance, tedious sample preparation procedures, or incompatibility with MS. More recently, hydrophilic interaction chromatography (HILIC) has been proposed as an alternative strategy for the analysis of 5FU 100,101,102 and cytidine analogues 103,104 as shown in Fig. 3.…”

Section: Antimetabolitesmentioning

confidence: 99%

Antineoplastic drugs and their analysis: a state of the art review

Guichard

Guillarme

Bonnabry

et al. 2017

Analyst

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The number of patients suffering from cancer is constantly increasing and, consequently, the number of different chemotherapy treatments administered is increasing. Given the high reactivity and toxicity of antineoplastic drugs, analytical methods are required in all pharmaceutical fields, from drug development to their elimination in wastewater; including formulation quality control, environment and human exposure and therapeutic drug monitoring. The aim of this paper is to provide an overview of the analytical methods available for the determination of antineoplastic drugs in different matrices such as pharmaceutical formulations, biological and environmental samples. The applicability and performance of the reported methods will be critically discussed, with focus on the most commonly used antineoplastic drugs. Only conventional compounds and small molecules for targeted therapy will be considered in the present review.

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

Cited by 57 publications

References 33 publications

5-Fluorouracil sensitivity varies among oral micro-organisms

5-Fluorouracil sensitivity varies among oral micro-organisms

Iontophoretic device delivery for the localized treatment of pancreatic ductal adenocarcinoma

Antineoplastic drugs and their analysis: a state of the art review

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