Fluorine-19 or phosphorus-31 NMR spectroscopy: A suitable analytical technique for quantitative in vitro metabolic studies of fluorinated or phosphorylated drugs

Martino, Robert; Gilard, Véronique; Desmoulin, Franck; Malet‐Martino, Myriam

doi:10.1016/j.jpba.2005.01.047

Cited by 91 publications

(69 citation statements)

References 71 publications

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“…The evaporative light scattering detector is useful in chemical purity assessment but too sensitive to biological matrix for ready use in metabolite quantification. Fluorine NMR can be a useful tool for quantitification of fluorine containing metabolites (76,77); while 1 H NMR may sometimes be useful (78). An interesting but preliminary approach is the hypothesis that mass spectral relative ionization efficiencies are more comparable in the nanoliter per minute spray range (58,79).…”

Section: Quantification Of Metabolitesmentioning

confidence: 99%

Analytical Tools and Approaches for Metabolite Identification in Early Drug Discovery

Chen¹,

Monshouwer²,

Fitch³

2006

Pharm Res

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Determination of the chemical structures of metabolites is a critical part of the early pharmaceutical discovery process. Understanding the structures of metabolites is useful both for optimizing the metabolic stability of a drug as well as rationalizing the drug safety profile. This review describes the current state of the art in this endeavor. The likely outcome of metabolism is first predicted by comparison to the literature. Then metabolites are synthesized in a variety of in vitro systems. The various approaches to LC/UV/MS are applied to learn information about these metabolites and structure hypotheses are made. Structures are confirmed by synthesis or NMR. The special topic of reactive metabolite structure determination is briefly addressed.

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Section: Quantification Of Metabolitesmentioning

confidence: 99%

Analytical Tools and Approaches for Metabolite Identification in Early Drug Discovery

Chen¹,

Monshouwer²,

Fitch³

2006

Pharm Res

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“…In the past, 19 F NMR has been used as an excellent tool for kinetic studies on chemical reactions [38,39].…”

Section: Introductionmentioning

confidence: 99%

Structural and Kinetic Considerations for the Application of the Traceless Staudinger Ligation to Future ¹⁸F Radiolabeling Using XRD and ¹⁹F NMR

Köckerling

Mamat

2017

Int J of Chemical Kinetics

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A 4-fluorobenzoate-functionalized phosphane was synthesized and reacted with different azides using the traceless Staudinger ligation as a representative sample reaction for future radiolabeling purposes with short-lived radionuclides like fluorine-18. For this purpose, the reaction rate was evaluated at different temperatures. The effect of starting material concentrations and the influence of the steric effect coming from the applied azides were investigated. 19 F NMR was used to determine the reaction half-live (τ 1/2 ) and the reaction rate constant (k obs ) of this ligation under mild reaction conditions in a water-acetonitrile mixture. Furthermore, the phosphane key compound 1 (orthorhombic, space group Pna2 1 , a = 18.6363(9), b = 8.3589(4), c = 18.5480(9)Å, V = 2889.4(2)Å 3 , Z = 8, D obs = 1.277 g/cm 3 ), which acts as starting material for all subsequent syntheses, and the fluorine-containing phosphane 3 (monoclinic, space group P2 1 /c, a = 8.321(2), b = 16.160(4), c = 14.940(4)Å, β = 99.51(1)°, V = 1981.4(8)Å 3 , Z = 4, D obs = 1.342 g/cm 3 ) were analyzed by single-crystal XRD.

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“…The pyrimidine 5-FU undergoes a complex metabolic pathway leading to the production of cytotoxic metabolites such as fluorouridine triphosphate and deoxyfluorouridine triphosphate that are respectively incorporated into RNA and DNA ( Fig. 1) [3]. Among the metabolites, 5-fluoro-2 -deoxyuridine-5 -monophosphate (5-FdUMP) plays a key role.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous quantification of 5-FU, 5-FUrd, 5-FdUrd, 5-FdUMP, dUMP and TMP in cultured cell models by LC-MS/MS

Carli

Honorat

Cohen

et al. 2009

Journal of Chromatography B

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Fluorine-19 or phosphorus-31 NMR spectroscopy: A suitable analytical technique for quantitative in vitro metabolic studies of fluorinated or phosphorylated drugs

Cited by 91 publications

References 71 publications

Analytical Tools and Approaches for Metabolite Identification in Early Drug Discovery

Analytical Tools and Approaches for Metabolite Identification in Early Drug Discovery

Structural and Kinetic Considerations for the Application of the Traceless Staudinger Ligation to Future ¹⁸F Radiolabeling Using XRD and ¹⁹F NMR

Simultaneous quantification of 5-FU, 5-FUrd, 5-FdUrd, 5-FdUMP, dUMP and TMP in cultured cell models by LC-MS/MS

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Fluorine-19 or phosphorus-31 NMR spectroscopy: A suitable analytical technique for quantitative in vitro metabolic studies of fluorinated or phosphorylated drugs

Cited by 91 publications

References 71 publications

Analytical Tools and Approaches for Metabolite Identification in Early Drug Discovery

Analytical Tools and Approaches for Metabolite Identification in Early Drug Discovery

Structural and Kinetic Considerations for the Application of the Traceless Staudinger Ligation to Future 18F Radiolabeling Using XRD and 19F NMR

Simultaneous quantification of 5-FU, 5-FUrd, 5-FdUrd, 5-FdUMP, dUMP and TMP in cultured cell models by LC-MS/MS

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Structural and Kinetic Considerations for the Application of the Traceless Staudinger Ligation to Future ¹⁸F Radiolabeling Using XRD and ¹⁹F NMR