当前位置： SCI文献检索 > CHEMICAL RESEARCH IN TOXICOLOGY期刊下所有文献 > Nuclear magnetic resonance spectroscopy as a quantitative tool to determine the concentrations of biologically produced metabolites: implications in metabolites in safety testing.

Nuclear magnetic resonance spectroscopy as a quantitative tool to determine the concentrations of biologically produced metabolites: implications in metabolites in safety testing.

Abstract：

:Nuclear magnetic resonance (NMR) spectroscopy has traditionally been considered as an indispensable tool in elucidating structures of metabolites. With the advent of Fourier transform (FT) spectrometers, along with improvements in software and hardware (such as high-field magnets, cryoprobes, versatile pulse sequences, and solvent suppression techniques), NMR is increasingly being considered as a critical quantitative tool, despite its lower sensitivity as compared to mass spectrometry. A specific quantitative application of NMR is in determining the concentrations of biologically isolated metabolites, which could potentially be used as reference standards for further quantitative work by liquid chromatography/mass spectrometry. With the recent demands from regulatory agencies on quantitative information on metabolites, it is proposed that NMR will play a significant role in strategies aimed at addressing metabolite coverage in toxicological species. Traditionally, biologically isolated metabolites have not been considered as a way of generating "reference standards" for further quantitative work. However, because of the recent FDA guidance on safety testing of metabolites, one has to consider means of authenticating and quantitating biologically or nonbiologically generated metabolites. 1H NMR is being proposed as the method of choice, as it is able to be used as both a qualitative and a quantitative tool, hence allowing structure determination, purity check, and quantitative measurement of the isolated metabolite. In this publication, the application of NMR as a powerful and robust analytical technique in determining the concentrations of in vitro or in vivo isolated metabolites is discussed. Furthermore, to demonstrate the reliability and accuracy of metabolite concentrations determined by NMR, validation and cross-validation with gravimetric and mass spectrometric methods were conducted.

journal_name

Chem Res Toxicol

journal_title

Chemical research in toxicology

authors

Espina R,Yu L,Wang J,Tong Z,Vashishtha S,Talaat R,Scatina J,Mutlib A

doi

10.1021/tx800251p

subject

Has Abstract

pub_date

2009-02-01 00:00:00

pages

299-310

issue

2

eissn

0893-228X

issn

1520-5010

journal_volume

22

pub_type

杂志文章

相关文献

CHEMICAL RESEARCH IN TOXICOLOGY文献大全
  • Identification of 14 quercetin phase II mono- and mixed conjugates and their formation by rat and human phase II in vitro model systems.

    abstract：:In this study, the HPLC, UV-vis, LC-MS, and 1H NMR characteristics of 14 different phase II mono- and mixed conjugates of quercetin were determined, providing a useful tool in the identification of quercetin phase II metabolite patterns in various biological systems. Using these data, the phase II metabolism of querce...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx049826v

    authors： van der Woude H,Boersma MG,Vervoort J,Rietjens IM

    更新日期：2004-11-01 00:00:00

  • Monitoring Cr intermediates and reactive oxygen species with fluorescent probes during chromate reduction.

    abstract：:Cr(VI) genotoxicity is caused by products of its reductive metabolism inside the cells. Reactive oxygen species (ROS) and Cr(V,IV) intermediates are potential sources of oxidative damage by Cr(VI). Here, we investigated seven fluorescent probes for the detection of ROS and non-ROS oxidants in Cr(VI) reactions with its...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx500028x

    authors： DeLoughery Z,Luczak MW,Zhitkovich A

    更新日期：2014-05-19 00:00:00

  • Abiotic sulfhydryl reactivity: a predictor of aquatic toxicity for carbonyl-containing alpha,beta-unsaturated compounds.

    abstract：:A diverse series of aliphatic alpha,beta-unsaturated esters, ketones, and aldehydes were evaluated for reactivity with the model nucleophile sulfhydryl group in the form of the cysteine residue of the tripeptide glutathione; the reactive end point (RC50) was then related to aquatic toxicity (IGC50) assessed in the Tet...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx600344a

    authors： Yarbrough JW,Schultz TW

    更新日期：2007-03-01 00:00:00

  • 1H NMR investigation of toxic effects of lindane and paraquat on Hep 3B and Hep G2 human hepatoma cell lines.

    abstract：:Lindane and paraquat induce biochemical changes in the liver. In order to specify their molecular impact at the cellular level, a 300 MHz 1H NMR investigation of hepatoma cell lines Hep 3B and Hep G2 responses was performed. Cells were exposed over 24 h to 50 mg/L lindane (0.178 mM) or to 100 mg/L (0.389 mM) paraquat ...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx9600309

    authors： Descampiaux B,Imbenotte M,Desenclos V,Vermeersch G,Lhermitte M,Erb F

    更新日期：1997-01-01 00:00:00

  • Effects of intracerebroventricular administration of 5-(glutathion-S-yl)-alpha-methyldopamine on brain dopamine, serotonin, and norepinephrine concentrations in male Sprague-Dawley rats.

    abstract：:alpha-Methyldopamine (alpha-MeDA) is a metabolite of the serotonergic neurotoxicants 3,4-(+/-)-(methylenedioxy)amphetamine (MDA) and 3,4-(+/-)-(methylenedioxy)methamphetamine (MDMA). alpha-MeDA readily oxidizes, and in the presence of glutathione (GSH) it forms 5-(glutathion-S-yl)-alpha-methyldopamine [5-(glutathion-S...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx9501546

    authors： Miller RT,Lau SS,Monks TJ

    更新日期：1996-03-01 00:00:00

  • Effects of Trichloroethylene on the Expression of Long Intergenic Noncoding RNAs in B6C3F1 Mouse Liver.

    abstract：:Trichloroethylene (TCE), a widely used industrial solvent, is a common environmental contaminant. We previously reported that TCE-induced changes in DNA methylation and miRNA expression contributed to the development of a liver tumor in mice. In this study, we investigated the role of long intergenic noncoding RNA (Li...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/acs.chemrestox.9b00382

    authors： Ren F,Wang J,Aniagu S,Li J,Jiang Y,Chen T

    更新日期：2020-06-15 00:00:00

  • The smoke produced from the oxidative pyrolysis of perfluoro polymers: an ESR spin-trapping study.

    abstract：:Spin adducts are observed when the unfiltered smoke produced during the aerobic pyrolysis of perfluoro polymers (PFP) is bubbled through a solution of the ESR spin trap alpha-phenyl-N-tert-butylnitrone (PBN). The spin adducts include those from an oxy radical and the fluorine atom, and in addition the spin trap is oxi...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx00009a009

    authors： Lachocki TM,Nuggehalli SK,Scherer KV,Church DF,Pryor WA

    更新日期：1989-05-01 00:00:00

  • Inhibition of doxorubicin chronic toxicity in catalase-overexpressing transgenic mouse hearts.

    abstract：:Catalase is an important antioxidant enzyme, which has been shown to provide cardiac protection from acute toxicity induced by doxorubicin, a most effective anticancer agent. Because cumulative dose-dependent chronic cardiomyopathy due to a long-term administration of doxorubicin is a significant clinical problem, the...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx015532n

    authors： Kang YJ,Sun X,Chen Y,Zhou Z

    更新日期：2002-01-01 00:00:00

  • Improved efficacy of acylfulvene in colon cancer cells when combined with a nuclear excision repair inhibitor.

    abstract：:The efficacy of DNA-damaging anticancer drugs is highly influenced by cellular DNA repair capacity, and by inhibiting the relevant DNA repair pathway, efficacy of alkylating agents may be increased. Therefore, combining DNA repair inhibitors with anticancer agents that selectively target tumor tissue should improve ca...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx400255f

    authors： van Midwoud PM,Sturla SJ

    更新日期：2013-11-18 00:00:00

  • Identification of tamoxifen-DNA adducts formed by alpha-sulfate tamoxifen and alpha-acetoxytamoxifen.

    abstract：:alpha-Sulfate trans-tamoxifen and alpha-sulfate cis-tamoxifen were synthesized as proposed active metabolites of tamoxifen that react with DNA. alpha-Acetoxytamoxifen was prepared as a model-activated form to produce a reactive carbocation. Calf thymus DNA was reacted with alpha-hydroxytamoxifen or the activated forms...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx960114h

    authors： Dasaradhi L,Shibutani S

    更新日期：1997-02-01 00:00:00

  • Accurate and efficient bypass of 8,5'-cyclopurine-2'-deoxynucleosides by human and yeast DNA polymerase η.

    abstract：:Reactive oxygen species (ROS), which can be produced during normal aerobic metabolism, can induce the formation of tandem DNA lesions, including 8,5'-cyclo-2'-deoxyadenosine (cyclo-dA) and 8,5'-cyclo-2'-deoxyguanosine (cyclo-dG). Previous studies have shown that cyclo-dA and cyclo-dG accumulate in cells and can block ...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx3001576

    authors： Swanson AL,Wang J,Wang Y

    更新日期：2012-08-20 00:00:00

  • Formation of hemoglobin and albumin adducts of benzene oxide in mouse, rat, and human blood.

    abstract：:Little is known about the formation and disposition of benzene oxide (BO), the initial metabolite arising from oxidation of benzene by cytochrome P450. In this study, reactions of BO with hemoglobin (Hb) and albumin (Alb) were investigated in blood from B6C3F1 mice, F344 rats, and humans in vitro. The estimated half-l...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx9701788

    authors： Lindstrom AB,Yeowell-O'Connell K,Waidyanatha S,McDonald TA,Golding BT,Rappaport SM

    更新日期：1998-04-01 00:00:00

  • Carbon Disulfide Induces Embryo Implantation Disorder by Disturbing the Polarization of Macrophages in Mice Uteri.

    abstract：:Carbon disulfide (CS2) induces embryo implantation disorders. Macrophages participate in the process of pregnancy. Therefore, we want to explore the effects of CS2 exposure on polarization and immune function of macrophages in pregnant mice uteri. The exposure times were gestation days 3 (GD3), 4 (GD4), and 5 (GD5), a...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/acs.chemrestox.9b00119

    authors： Zhang T,Hu C,Wu Y,Wang S,Liu X,Zhang D,Huang F,Gao H,Wang Z

    更新日期：2019-10-21 00:00:00

  • DNA adducts from nitroreduction of 2,7-dinitrofluorene, a mammary gland carcinogen, catalyzed by rat liver or mammary gland cytosol.

    abstract：:Nitrofluorenes are mutagenic and carcinogenic environmental pollutants arising chiefly from combustion of fossil fuels. Nitro aromatic compounds undergo nitroreduction to N-hydroxy arylamines that bind to DNA directly or after O-esterification. This study analyzes the DNA binding and adducts from the in vitro nitrored...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx010172p

    authors： Ritter CL,Culp SJ,Freeman JP,Marques MM,Beland FA,Malejka-Giganti D

    更新日期：2002-04-01 00:00:00

  • Effect of the peroxisome proliferator perfluoro-n-decanoic acid on glucose transport in the isolated perfused rat liver.

    abstract：:The perfluorinated carboxylic acid, perfluoro-n-decanoic acid (PFDA), is a known peroxisome proliferator which displays toxicity in rodents. Using a paired-tracer first-pass extraction technique, the effect of PFDA on hepatic glucose transport was determined in the isolated perfused rat liver. In brief, livers isolate...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx00043a010

    authors： Goecke-Flora CM,Wyman JF,Jarnot BM,Reo NV

    更新日期：1995-01-01 00:00:00

  • The Impact of the COVID-19 Pandemic on the Future of Science Careers.

    abstract：:As COVID-19 swept across the world, it created a global pandemic and an unpredictable and challenging job market. This article discusses the future of the 2020-2021 job market in both academia and industry in the midst and aftermath of this pandemic. ...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/acs.chemrestox.0c00436

    authors： Perera HM,Griffin WC,Kankanamage RNT,Pathira Kankanamge LS

    更新日期：2020-12-23 00:00:00

  • Chemical speciation of trivalent actinides and lanthanides in biological fluids: the dominant in vitro binding form of curium(III) and europium(III) in human urine.

    abstract：:Radionuclides represent a serious health risk to humans in the case of incorporation. To elucidate the potential of time-resolved laser-induced fluorescence spectroscopy (TRLFS) to determine the dominant radionuclide species in natural biofluids, we investigated the in vitro speciation of curium(III) in human urine sa...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx100273g

    authors： Heller A,Barkleit A,Bernhard G

    更新日期：2011-02-18 00:00:00

  • Base sequence-dependent bends in site-specific benzo[a]pyrene diol epoxide-modified oligonucleotide duplexes.

    abstract：:The site specifically modified oligonucleotides 5'-d(TCCTCCTG1G2CCTCTC) (I) and 5'-d(CTATG1G2G3TATC) (II) were synthesized with single modified guanine residues at positions G1, G2, or G3, derived from the covalent binding reaction of 7R,8S-dihydroxy-9S,10R-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene ((+)-anti-BPDE) with ...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx9501086

    authors： Liu T,Xu J,Tsao H,Li B,Xu R,Yang C,Amin S,Moriya M,Geacintov NE

    更新日期：1996-01-01 00:00:00

  • Trends in Environmental Tobacco Smoke (ETS) Exposure and Preterm Birth: Use of Smoking Bans and Direct ETS Exposure Assessments in Study Designs.

    abstract：:For decades, many studies have linked maternal smoking to an increased risk of preterm birth. As a result, the scientific community has long hypothesized that exposure to environmental tobacco smoke (ETS), commonly referred to as second-hand smoke, is also associated with an increased risk of preterm birth. Multiple s...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/acs.chemrestox.7b00054

    authors： Elkin ER,O'Neill MS

    更新日期：2017-07-17 00:00:00

  • Peroxynitrite-initiated oxidation of acetoacetate and 2-methylacetoacetate esters by oxygen: potential sources of reactive intermediates in keto acidoses.

    abstract：:Oxidative stress is believed to play a role in the pathogenesis of several diseases, including diabetes and inborn errors of metabolism. The types of oxidative damage observed in these pathologies have been attributed to the excessive production of reactive intermediates relating to the accumulation of toxic metabolit...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx049821y

    authors： Royer LO,Knudsen FS,de Oliveira MA,Tavares MF,Bechara EJ

    更新日期：2004-12-01 00:00:00

  • Decomposition rates of isothiocyanate conjugates determine their activity as inhibitors of cytochrome p450 enzymes.

    abstract：:Thiol conjugates of isothiocyanates (thiol-ITCs) are metabolites of ITCs formed in the mercapturic acid pathway in mammals. They are effective chemopreventive agents in mouse lung tumor bioassays and in other models. Thiol-ITCs are inhibitors of P450s, but it has not been determined if P450 inhibition is due to conjug...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx010029w

    authors： Conaway CC,Krzeminski J,Amin S,Chung FL

    更新日期：2001-09-01 00:00:00

  • Indirect cytotoxicity of flucloxacillin toward human biliary epithelium via metabolite formation in hepatocytes.

    abstract：:Flucloxacillin, an isoxazolyl-penicillin, causes cholestasis and biliary epithelium injury. The aim of the study was to determine whether flucloxacillin, either directly or through metabolite formation, may induce cytotoxicity in hepatic or biliary cells. Cytotoxicity was assessed by lactate dehydrogenase release in p...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx0002435

    authors： Lakehal F,Dansette PM,Becquemont L,Lasnier E,Delelo R,Balladur P,Poupon R,Beaune PH,Housset C

    更新日期：2001-06-01 00:00:00

  • Aromatic Residues at the Dimer-Dimer Interface in the Peroxiredoxin Tsa1 Facilitate Decamer Formation and Biological Function.

    abstract：:To prevent the accumulation of reactive oxygen species and limit associated damage to biological macromolecules, cells express a variety of oxidant-detoxifying enzymes, including peroxiredoxins. In Saccharomyces cerevisiae, the peroxiredoxin Tsa1 plays a key role in peroxide clearance and maintenance of genome stabili...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/acs.chemrestox.8b00346

    authors： Loberg MA,Hurtig JE,Graff AH,Allan KM,Buchan JA,Spencer MK,Kelly JE,Clodfelter JE,Morano KA,Lowther WT,West JD

    更新日期：2019-03-18 00:00:00

  • Mechanisms of nitrogen oxide-mediated disruption of metalloprotein function: an examination of the copper-responsive yeast transcription factor Ace1.

    abstract：:Nitric oxide (NO) has been found to inhibit the copper-responsive yeast transcription factor Ace1 in an oxygen-dependent manner. However, the mechanism responsible for NO-dependent inhibition of Ace1 remains unestablished. In the present study, the chemical interaction of nitrogen oxide species with Ace1 was examined ...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx010102i

    authors： Shinyashiki M,Pan CJ,Switzer CH,Fukuto JM

    更新日期：2001-12-01 00:00:00

  • Particulate depleted uranium is cytotoxic and clastogenic to human lung cells.

    abstract：:Depleted uranium (DU) is commonly used in military armor and munitions, and thus, exposure of soldiers and non-combatants is potentially frequent and widespread. DU is considered a suspected human carcinogen, affecting the bronchial cells of the lung. However, few investigations have studied DU in human bronchial cell...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx700026r

    authors： Wise SS,Thompson WD,Aboueissa AM,Mason MD,Wise JP Sr

    更新日期：2007-05-01 00:00:00

  • A kinetic model of the cell culture cytotoxicity of metabolically activated agents: N-methyl-N-(acetoxymethyl)nitrosamine, methylnitrosourethane, and (methylazoxy)methanol acetate.

    abstract：:The activity of three metabolically activated methylating agents, N-methyl-N-(acetoxymethyl)nitrosamine (DMN-OAc), methylnitrosourethane (MNUT), and (methylazoxy)methanol acetate (MAM-Ac), were determined in cell culture by using a P388 cell growth rate inhibition assay. Experiments were conducted with normal P388 cel...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx00011a004

    authors： Weinkam RJ,Plakunov I

    更新日期：1989-09-01 00:00:00

  • Potent mutagenicity of 3-methylindole requires pulmonary cytochrome P450-mediated bioactivation: a comparison to the prototype cigarette smoke mutagens B(a)P and NNK.

    abstract：:3-Methylindole (3MI) is a preferential pneumotoxicant found in cigarette smoke. A number of lung-expressed human cytochrome P450 enzymes, including 1A1, 2F1, and 2A13, catalyze the metabolism of 3MI to reactive intermediates that fragment DNA, measured with the Comet assay to assess DNA damage, in a cytochrome P450-de...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx100147z

    authors： Weems JM,Lamb JG,D'Agostino J,Ding X,Yost GS

    更新日期：2010-11-15 00:00:00

  • Arsenic exposure through drinking water is associated with longer telomeres in peripheral blood.

    abstract：:Inorganic arsenic is a strong carcinogen, possibly by interaction with the telomere length. The aim of the study was to evaluate how chronic arsenic exposure from drinking water as well as the arsenic metabolism efficiency affect the individual telomere length and the expression of telomere-related genes. Two hundred ...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx300222t

    authors： Li H,Engström K,Vahter M,Broberg K

    更新日期：2012-11-19 00:00:00

  • Nanomaterials and Innate Immunity: A Perspective of the Current Status in Nanosafety.

    abstract：:Human exposure to engineered nanomaterials (ENMs) is inevitable due to the plethora of applications for which they are being manufactured and integrated within. ENMs demonstrate plentiful advantages in terms of industrial approaches as well as from a consumer perspective. However, despite such positives, doubts remain...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/acs.chemrestox.0c00051

    authors： Cronin JG,Jones N,Thornton CA,Jenkins GJS,Doak SH,Clift MJD

    更新日期：2020-05-18 00:00:00

  • AHR- and DNA-damage-mediated gene expression responses induced by benzo(a)pyrene in human cell lines.

    abstract：:Carcinogens induce complex transcriptional responses in cells that may hold key mechanistic information. Benzo(a)pyrene (BaP) modulation of transcription may occur through the activation of the aryl hydrocarbon receptor (AHR) or through responses to DNA damage. To characterize further the expression profiles induced b...

    journal_title：Chemical research in toxicology

    pub_type： 杂志文章

    doi：10.1021/tx700252n

    authors： Hockley SL,Arlt VM,Brewer D,Te Poele R,Workman P,Giddings I,Phillips DH

    更新日期：2007-12-01 00:00:00