14C AMS quantification of biomolecular interactions using microbore and plate separations

Creek, Moire R.; Frantz, Chris; Fultz, Esther; Haack, Kurt; Redwine, K.; Shen, Nancy H.; Turteltaub, Ken W; Vogel, John S.

doi:10.1016/0168-583x(94)96053-4

Cited by 11 publications

(7 citation statements)

References 4 publications

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“…Quantitative metabolic profiles in plasma or urine are obtained by comparing the isotopic concentration of the injected sample with the sum of the eluted isotope profile to correct for any analytical losses. Several different components add to the backgrounds of LC/AMS, and total column loading should be held under 10 fmol total 14 C [1 disintegration per minute (dpm)] to avoid valve or column contaminations in succeeding analyses (36). Simple fraction collection can be used to obtain the kinetics of the separate species, if there are only a few established metabolites as with carotene metabolism, but even low resolution (1 min) fractions often reveal sufficient detail to determine changes in major metabolites and the presence of previously unnoticed products.…”

Section: Lc/ams Metabolic Profilesmentioning

confidence: 99%

Accelerator Mass Spectrometry for Quantitative in Vivo Tracing

Vogel¹

2005

BioTechniques

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66Manuscript: 2910 AbstractAccelerator mass spectrometry (AMS) counts individual rare, usually radio-, isotopes such as radiocarbon at high efficiency and specificity in milligram-sized samples. AMS traces very low chemical doses (µg) and radiative doses (100 Bq) of isotope labeled compounds in animal models and directly in humans for pharmaceutical, nutritional, or toxicological research.Absorption, metabolism, distribution, binding, and elimination are all quantifiable with high precision after appropriate sample definition.

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Section: Lc/ams Metabolic Profilesmentioning

confidence: 99%

Accelerator Mass Spectrometry for Quantitative in Vivo Tracing

Vogel¹

2005

BioTechniques

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“…For the remainder of the samples, the urine was first diluted 10× in distilled water, and 25 μL of diluted urine was added to the carrier solution. The methanol and water were removed by vacuum centrifugation .…”

Section: Methodsmentioning

confidence: 99%

“…Accelerator mass spectrometry was developed to detect 14 C levels orders of magnitude below modern natural abundance with high precision and accuracy for radiocarbon dating, and AMS is more sensitive than LSC for the detection of 14 C by factors of 10 5 −10 6 . Several studies concerning the use of AMS for 14 C detection of samples from in vivo studies in test animals − and humans 29 have been reported.…”

mentioning

confidence: 99%

Analytical Performance of Accelerator Mass Spectrometry and Liquid Scintillation Counting for Detection of ¹⁴C-Labeled Atrazine Metabolites in Human Urine

et al. 1998

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Accelerator mass spectrometry (AMS) has been applied to the detection of 14C-labeled urinary metabolites of the triazine herbicide, atrazine, and the analytical performance of AMS has been directly compared to that of liquid scintillation counting (LSC). Ten human subjects were given a dermal dose of 14C-labeled atrazine over 24 h, and urine from the subjects was collected over a 7-day period. Concentrations of 14C in the samples have been determined by AMS and LSC and range from 1.8 fmol/mL to 4.3 pmol/mL. Data from these two methods have a correlation coefficient of 0.998 for a linear plot of the entire sample set. Accelerator mass spectrometry provides superior concentration (2.2 vs 27 fmol/mL) and mass (5.5 vs 54,000 amol) detection limits relative to those of LSC for these samples. The precision of the data provided by AMS for low-level samples is 1.7%, and the day-to-day reproducibility of the AMS measurements is 3.9%. Factors limiting AMS detection limits for these samples and ways in which these can be improved are examined.

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“…DNA adduct analysis by AMS at these low isotope ratios can be done with lower specific activities and smaller quantities of isotope than has been practical with decay counting [Vogel et al, 1990;Vogel and Turteltaub, 1992;Turteltaub et al, 1995]. It is particularly useful for analysis of DNA digests, when separation and analysis of specific DNA adducts is necessary, or when there is a need to be able to detect DNA adducts at levels below 1 adduct per 10 9 nucleotides [Creek et al, 1994]. This may be necessary to show that a compound does not bind DNA.…”

Section: Strengthsmentioning

confidence: 99%

Methods of DNA adduct determination and their application to testing compounds for genotoxicity

Phillips¹,

Farmer²,

Beland³

et al. 2000

Environ. Mol. Mutagen.

137

110

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At the International Workshop on Genotoxicity Test Procedures (IWGTP) held in Washington, DC (March 25–26, 1999), a working group considered the uses of DNA adduct determination methods for testing compounds for genotoxicity. When a drug or chemical displays an unusual or inconsistent combination of positive and negative results in in vitro and in vivo genotoxicity assays and/or in carcinogenicity experiments, investigations into whether or not DNA adducts are formed may be helpful in assessing whether or not the test compound is a genotoxin. DNA adduct determinations can be carried out using radiolabeled compounds and measuring radioactive decay (scintillation counting) or isotope ratios (accelerator mass spectrometry) in the isolated DNA. With unlabeled compounds adducts may be measured by 32P‐postlabeling analysis of the DNA, or by physicochemical methods including mass spectrometry, fluorescence spectroscopy, or electrochemical detection, or by immunochemical methods. Each of these approaches has different strengths and limitations, influenced by sensitivity, cost, time, and interpretation of results. The design of DNA binding studies needs to be on a case‐by‐case basis, depending on the compound's profile of activity. DNA purity becomes increasingly important the more sensitive, and less chemically specific, the assay. While there may be adduct levels at which there is no observable biological effect, there are at present insufficient data on which to set a threshold level for biological significance. Environ. Mol. Mutagen. 35:222–233, 2000 © 2000 Wiley‐Liss, Inc.

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14C AMS quantification of biomolecular interactions using microbore and plate separations

Cited by 11 publications

References 4 publications

Accelerator Mass Spectrometry for Quantitative in Vivo Tracing

Accelerator Mass Spectrometry for Quantitative in Vivo Tracing

Analytical Performance of Accelerator Mass Spectrometry and Liquid Scintillation Counting for Detection of ¹⁴C-Labeled Atrazine Metabolites in Human Urine

Methods of DNA adduct determination and their application to testing compounds for genotoxicity

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14C AMS quantification of biomolecular interactions using microbore and plate separations

Cited by 11 publications

References 4 publications

Accelerator Mass Spectrometry for Quantitative in Vivo Tracing

Accelerator Mass Spectrometry for Quantitative in Vivo Tracing

Analytical Performance of Accelerator Mass Spectrometry and Liquid Scintillation Counting for Detection of 14C-Labeled Atrazine Metabolites in Human Urine

Methods of DNA adduct determination and their application to testing compounds for genotoxicity

Contact Info

Product

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Analytical Performance of Accelerator Mass Spectrometry and Liquid Scintillation Counting for Detection of ¹⁴C-Labeled Atrazine Metabolites in Human Urine