Quantitative NMR in synthetic and combinatorial chemistry

Rizzo, Vincenzo; Pinciroli, Vittorio

doi:10.1016/j.jpba.2005.01.045

Cited by 98 publications

(81 citation statements)

References 31 publications

(59 reference statements)

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“…After careful manual phase and baseline corrections, the intensities were determined by integrating the signal areas in a region extended at 30 times the line-width (about 70 Hz) each side of the peak [21]. To evaluate the standard deviations, the intensities were either used as such or normalized to the intensity of the ERETICä signal.…”

Section: Data Processingmentioning

confidence: 99%

Precision and sensitivity optimization of quantitative measurements in solid state NMR

Ziarelli

Viel

Sanchez

et al. 2007

Journal of Magnetic Resonance

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Section: Data Processingmentioning

confidence: 99%

Precision and sensitivity optimization of quantitative measurements in solid state NMR

Ziarelli

Viel

Sanchez

et al. 2007

Journal of Magnetic Resonance

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“…Since qNMR is well established in liquid-state NMR [1,2] here we focus on quantification of solid-state NMR spectra. Under typical conditions the sensitivity of the NMR experiment is rather limited which does not make NMR a likely candidate for trace analysis where the analyte is below 1% in concentration.…”

Section: Introductionmentioning

confidence: 99%

A method for improved quantification of 1H NMR signals under low-resolution conditions for solids

Avadhut

Schneider

Günne

2009

Journal of Magnetic Resonance

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“…In response to the demands from regulatory agencies to better define the exposures of metabolites in humans and in preclinical species (U.S. Food and Drug Administration, 2008), strategies based on the application of NMR as a quantitative tool for metabolite quantitation have been proposed (Dear et al, 2008;Espina et al, 2009). NMR was used in the past as an analytical tool to determine concentrations of synthetic and biosynthetic products (Warren et al, 1976;Vinson and Kozak, 1978;Werner et al, 1997;Groen et al, 1998;Silvestre et al, 2001;Holzgrabe et al, 2005;Pauli et al, 2005Pauli et al, , 2007Pauli et al, , 2008Rizzo and Pinciroli, 2005;Diehl et al, 2007;Shao et al, 2007), metabolites, catabolites, and endogenous compounds in biological fluids (MaletMartino et al, 1986;Monté et al, 1994;Desmoulin et al, 2002;Orhan et al, 2004;Skordi et al, 2004;Moazzami et al, 2007), or impurities present in products (Hays, 2005;Malz and Jancke, 2006). The theoretical aspects and validation of quantitative NMR have been discussed and reviewed in the literature (Mackenzie, 1984;Evilia, 2001;Burton et al, 2005;Malz and Jancke, 2005).…”

Section: Discussionmentioning

confidence: 99%

Application of Quantitative NMR in Pharmacological Evaluation of Biologically Generated Metabolites: Implications in Drug Discovery

et al. 2010

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ABSTRACT:It is important to gain an understanding of the pharmacological activities of metabolite(s) of compounds in development, especially if they are found in systemic circulation in humans. Pharmacological evaluation of metabolites is normally conducted with synthetic standards, which become available during various stages of drug development. However, the synthesis of metabolite standards may be protracted, taking anywhere from several weeks to months to be completed. This often slows down early pharmacological evaluation of metabolites. Once a metabolite(s) is found to possess comparable (or greater) pharmacological activity than the parent compound, additional studies are performed to better understand the implications of circulating pharmacologically active metabolite(s). To conduct some of these studies as early as possible without slowing the progression of a compound in development is important, especially if critical go or no-go decisions impinge on the outcomes from these studies. Early pharmacological evaluation of significant metabolites is hereby proposed to be conducted in the drug discovery stage so that all pertinent studies and information can be gathered in a timely manner for decisionmaking. It is suggested that these major metabolites be isolated, either from biological or chemical sources, and quantified appropriately. For biologically generated metabolites, NMR is proposed as the tool of choice to quantitate these metabolites before their evaluation in pharmacological assays. For metabolites that have the same UV characteristics as the parent compound, quantitation can be conducted using UV spectroscopy instead of NMR. In this article, we propose a strategy that could be used to determine the pharmacological activities of metabolites isolated in submilligram quantities.

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Quantitative NMR in synthetic and combinatorial chemistry

Cited by 98 publications

References 31 publications

Precision and sensitivity optimization of quantitative measurements in solid state NMR

Precision and sensitivity optimization of quantitative measurements in solid state NMR

A method for improved quantification of 1H NMR signals under low-resolution conditions for solids

Application of Quantitative NMR in Pharmacological Evaluation of Biologically Generated Metabolites: Implications in Drug Discovery

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