Preparation and mass spectral characterization of pentafluorobenzyl derivatives of alkyl and hydroxyalkyl-nucleobase DNA adducts

Saha, Manasi; Kresbach, Gerhard M.; Giese, Roger W.; Annan, Roland S.; Vouros, Paul

doi:10.1002/bms.1200181103

Cited by 19 publications

(16 citation statements)

References 27 publications

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“…Aside from octafluoronaphthalene (OFN), the structures of the compounds tested in this work are shown in Figure 1. They are of interest to us as analyte products derived from DNA adducts (9,10,12). Each of these compounds gives a strong response (see below) by gas chromatography with electron capture negative-ion mass spectrometry with selected-ion monitoring, in part because the ECNI spectrum of each is dominated by a single ion.…”

Section: Resultsmentioning

confidence: 99%

Gas chromatography/electron capture negative-ion mass spectrometry at the zeptomole level

Abdel-Baky¹,

Giese²

1991

Anal. Chem.

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Twelve years ago, Hunt and Crow demonstrated that 20-50-amol amounts of strong electophores could be detected with a Finnigan quadrupole gas chromatograph/electron capture negative-ion mass spectrometer GC/ECNI-MS (1). These measurements were made after the conditions in the instrument were optimized for high sensitivity: electron energy 100 eV, methane reagent gas pressure 0.6-0.8 Torr, and source temperature 100-150 °C. Unremarkably, it would seem, nearly the same conditions are recommended by the manufacturer (Hewlett-Packard) for optimum sensitivity of the quadrupole ECNI-MS that we possess, based on testing the instrument with the prescribed electrophore, octafluoronaphthalene (OFN). However, it has been established that the response in ECNI is subject to many variables, including compound tested, type of instrument, and several parameters of the ion source (2-6). Thus we considered that it was worthwhile to tune our GC/ECNI-MS for the electrophoric analytes of interest in our laboratory. As reported here, such tuning leads to a set of conditions which significantly increase the S/N for these latter types of compounds, but only a little for OFN.

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Section: Resultsmentioning

confidence: 99%

Gas chromatography/electron capture negative-ion mass spectrometry at the zeptomole level

Abdel-Baky¹,

Giese²

1991

Anal. Chem.

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“…The GC-EC/MS equipment has been described before,1 as has the NMR. 3 Synthesis. 2-Fluoro-0*-methylhypoxanthine.…”

Section: Methodsmentioning

confidence: 99%

“…Ethyl acetate was used to wash the solid, and the filtrate was evaporated, followed by preparative TLC using ethyl acetate/hexane (1:1). Product 12: R¡ = 0.33; 1.9 mg, 15.5% yield; NMR (CDCla) 8.10 (s, 1H), 5.67 (s, 2H), 4.70 (t, 2H), 3.78 (t, 2H), 1.26 (s, 9H). Product 11: Rf = 0.66; 6.6 mg, 53.7% yield); NMR (CDC13) 7.94 (s, 1H), 5.45 (s, 2H), 4.68 (t, 2H), 3.80 (t, 2H), 1.26 (s, 9H).…”

Section: -Fluoro-of-[2'-(tert-butyloxymentioning

confidence: 99%

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Chemical transformation/derivatization of O6-methyl- and O6-(hydroxyethyl)guanine for detection by GC-EC/MS

Chiu

Saha²,

Abushamaa³

et al. 1993

Anal. Chem.

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In this project we set out to make an important class of DNA adducts, comprising O6-alkyl and O6-(hydroxyalkyl)guanines, susceptible to sensitive detection by GC-EC/MS. While existing literature indicated that pentafluorobenzylation would be useful for the ring NH site on these compounds, how to best overcome the polarity of the exocyclic NH2 and OH groups, without losing the O6-alkyl moiety, was less clear. Working with O6-methylguanine and O6-(2'-hydroxyethyl)guanine as representative analytes, we found that the NH2 group could be converted into fluoro without loss of the O6 substituent. For the OH group, a comparison of several derivatives (OR') led to R' = tert-butyl as the best choice at this stage. The latter work, especially via NMR, also allowed exact structural assignments to be made for the N7 and N9 pentafluorobenzyl isomeric derivatives that formed. Of these R' derivatives, the N7 isomers migrated slower on silica-TLC, had higher GC retention times, had lower responses by GC-EC/MS, and were preferentially destroyed as the GC column aged. However, the N9 isomer was slower on TLC when the OH was not derivatized. This behavior was rationalized using a concept of "polar footprint" for the derivatives. The concept also seemed to explain the puzzling GC-EC/MS behavior of some related compounds in our laboratory. Apparently the polar footprint should be minimized in designing derivatives for trace detection by GC-EC/MS.

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“…Analysis of the PFB-derivative with electron-capture negative chemicalionization mass spectrometry (ECNCI-MS) in full-scan mode yields the most-abundant anion [M À 181] À ions at m/z ¼ 555 for N7-HEG and m/z ¼ 559 for the d 4 -labeled N7-HEG by the loss of one PFBBr group (Saha, Abushamaa, & Giese, 1995). By monitoring the most-abundant fragment ion, GC/ECNCI-MS SIM analysis of this derivative demonstrated excellent sensitivity and specificity for quantification of N7-HEG (Saha et al, 1989;Allam, Saha, & Giese, 1990). An on-column detection limit of 1.3 amol (1 Â 10 À18 mol) was reported at a signal-to-noise ratio of 13 (Abdel-Baky & Giese, 1991).…”

Section: B Gc/ms Analysis Of Eo-induced Dna Adductsmentioning

confidence: 98%

The application of mass spectrometry in molecular dosimetry: Ethylene oxide as an example

Chiang

Shih

et al. 2011

Mass Spectrometry Reviews

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Mass spectrometry plays an increasingly important role in the search for and quantification of novel chemically specific biomarkers. The revolutionary advances in mass spectrometry instrumentation and technology empower scientists to specifically analyze DNA and protein adducts, considered as molecular dosimeters, derived from reactions of a carcinogen or its active metabolites with DNA or protein. Analysis of the adducted DNA bases and proteins can elucidate the chemically reactive species of carcinogens in humans and can serve as risk-associated biomarkers for early prediction of cancer risk. In this article, we review and compare the specificity, sensitivity, resolution, and ease-of-use of mass spectrometry methods developed to analyze ethylene oxide (EO)-induced DNA and protein adducts, particularly N7-(2-hydroxyethyl)guanine (N7-HEG) and N-(2-hydroxyethyl)valine (HEV), in human samples and in animal tissues. GC/ECNCI-MS analysis after HPLC cleanup is the most sensitive method for quantification of N7-HEG, but limited by the tedious sample preparation procedures. Excellent sensitivity and specificity in analysis of N7-HEG can be achieved by LC/MS/MS analysis if the mobile phase, the inlet (split or splitless), and the collision energy are properly optimized. GC/ECNCI-HRMS and GC/ECNCI-MS/MS analysis of HEV achieves the best performance as compared with GC/ECNCI-MS and GC/EI-MS. In conclusion, future improvements in high-throughput capabilities, detection sensitivity, and resolution of mass spectrometry will attract more scientists to identify and/or quantify novel molecular dosimeters or profiles of these biomarkers in toxicological and/or epidemiological studies.

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Preparation and mass spectral characterization of pentafluorobenzyl derivatives of alkyl and hydroxyalkyl-nucleobase DNA adducts

Cited by 19 publications

References 27 publications

Gas chromatography/electron capture negative-ion mass spectrometry at the zeptomole level

Gas chromatography/electron capture negative-ion mass spectrometry at the zeptomole level

Chemical transformation/derivatization of O6-methyl- and O6-(hydroxyethyl)guanine for detection by GC-EC/MS

The application of mass spectrometry in molecular dosimetry: Ethylene oxide as an example

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