Liquid chromatography–mass spectrometry in nucleoside, nucleotide and modified nucleotide characterization

Esmans, Eddy L.; Broes, D; Hoes, I.; Lemière, Filip; Vanhoutte, Koen

doi:10.1016/s0021-9673(97)00902-3

Cited by 82 publications

(64 citation statements)

References 90 publications

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“…Because of its sensitivity and specificity, mass spectrometry appears to be a powerful tool for exploring this field of investigation [20 -22]. Moreover, the possibility of on-line coupling with separation techniques, such as HPLC or CE, enhances the detection capabilities of this method [23][24][25]. Among different soft desorption-ionization techniques (e.g., MALDI, FAB, TSP), electrospray ionization is now commonly used for DNA adduct analysis, because of the very soft desolvation conditions which avoid fragile bond cleavages.…”

mentioning

confidence: 99%

Investigation of the regio- and stereo-selectivity of deoxyguanosine linkage to deuterated 2-hydroxyestradiol by using liquid chromatography/ESI-ion trap mass spectrometry

Debrauwer

Rathahao

Jouanin

et al. 2003

J. Am. Soc. Mass Spectrom.

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From previous studies on the reactivity of estradiol 2,3-quinone towards deoxyribonucleosides, it was demonstrated that several isomeric adducts were formed. Although adduction on steroid ring A or B has been evidenced using sequential MS n experiments, in some cases attachment positions are difficult to identify unambiguously. In this work, 2-hydroxyestradiol labeled with deuterium at various positions [6␤ (1); 6␣-7␣ (2); 6␣-6␤-7␣ (3)] have been used. Isomeric adduct differentiation could be achieved using LC-ESI-MS n . The m/z shift of the quasi-molecular ions as well as the fragmentation pathways suggested that adduction could occur on both C6 and C9 sites of the steroid B ring: Nucleophilic attack of the base on the C6 position of the steroid led to major adducts and addition of the base on the activated C9 site gave minor adducts that were found to be unstable. LC-MS n experiments carried out under deuterated medium provided information about some fragmentation processes by studying the m/z shift of fragment ions: (1) the loss of deoxyribose from the quasi-molecular ions took place according to a process involving a deuterium transfer from the deoxyribose alcohol function; (2) the cleavage of the steroid-base linkage involved a deuterium transfer from the hydroxy group of the catechol and likely occurred via the formation of an ion-dipole complex. The model studies conducted in this work provide new information on the fragmentation mechanisms of covalent adducts formed from estrogen quinones and deoxyguanosine, the most reactive DNA base. Besides, the first unequivocal characterization of adducts involving the steroid C9 position is shown by using deuterium labeled estrogen quinones. (J Am Soc Mass Spectrom 2003, 14, 364 -372)

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confidence: 99%

Investigation of the regio- and stereo-selectivity of deoxyguanosine linkage to deuterated 2-hydroxyestradiol by using liquid chromatography/ESI-ion trap mass spectrometry

Debrauwer

Rathahao

Jouanin

et al. 2003

J. Am. Soc. Mass Spectrom.

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“…Singh and Farmer [34], with particular reference to electrospray ionisation (ESI)-liquid chromatography (LC)-MS, Esmans et al [35] Andrews et al [36], Doerge et al [37], Koc and Swenberg [38] and Watson et al [39]. The approaches most usually employ collision induced dissociation (CID) tandem MS (MS/MS) with selected reaction monitoring (SRM) for the determination of:…”

Section: Use Of Mass Spectrometry (Ms) In Dna Adduct Detectionmentioning

confidence: 99%

Use of DNA adducts to identify human health risk from exposure to hazardous environmental pollutants: The increasing role of mass spectrometry in assessing biologically effective doses of genotoxic carcinogens

Farmer

Singh

2008

Mutation Research/Reviews in Mutation Research

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“…This treatment is expected to result in hydrolysis of the adduct. During the last decade there has been a large increase in the use of LC coupled to mass-spectrometric detection for direct analysis of DNA-base adducts [14,15]. In addition, applying several new techniques such as miniaturization of LC and column switching enables analysis of low levels of DNA adducts in complex biological matrices [16].…”

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confidence: 99%

Analysis of DNA-phosphate adducts in vitro using miniaturized LC-ESI-MS/MS and column switching: Phosphotriesters and alkyl cobalamins

Haglund

Dongen

Lemière

et al. 2004

J Am Soc Mass Spectrom

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Belgium DNA-phosphate adducts are known to be formed by a variety of alkylating agents. Due to little or no repair of DNA-phosphate adducts, these adducts may offer increased possibilities of both identifying and quantifying DNA adducts. The formation of DNA-phosphate adducts leads to a complete esterification of the phosphate group giving rise to a phosphotriester configuration. This work consists of the characterization of ethyl phosphotriesters (Ethyl PTE) using miniaturized LC-ESI-MS/MS and column switching in enzymatic hydrolysate of DNA treated in vitro with the model compound N-ethyl-N-nitrosourea (ENU). In vitro ENU-treated DNA was enzymatically degraded using nuclease P1, phosphodiesterase, and alkaline phosphatase. The use of column switch allowed for large-volume injections, where unmodified nucleosides were discarded in the loading step. The analytes were forward flushed to the analytical column in the eluting step and separated using a linear gradient. Ten different ethyl PTEs (dGpEtdG, dApEtdA, dCpEtdC, TpEtT, dGpEtdA, dGpEtdC, dGpEtT, dApEtdC, dApEtT, and dCpEtT) were characterized by their masses and CAD product ion spectra. Measurements of accurate masses were carried out yielding experimental masses within 5 ppm of the calculated masses for 9 of the 10 ethyl PTEs. For comparison, the enzymatic hydrolysate of ENU-treated DNA was subjected to transalkylation of the DNA-phosphate adducts by cob(I)alamin. Formed ethyl-cobalamins were analyzed according to earlier developed methods. The limit of detection of an alkyl-cobalamin standard and an alkyl PTE standard was 2 fmol and 5 fmol, respectively. (J Am Soc Mass Spectrom 2004, 15, 593-606)

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Liquid chromatography–mass spectrometry in nucleoside, nucleotide and modified nucleotide characterization

Cited by 82 publications

References 90 publications

Investigation of the regio- and stereo-selectivity of deoxyguanosine linkage to deuterated 2-hydroxyestradiol by using liquid chromatography/ESI-ion trap mass spectrometry

Investigation of the regio- and stereo-selectivity of deoxyguanosine linkage to deuterated 2-hydroxyestradiol by using liquid chromatography/ESI-ion trap mass spectrometry

Use of DNA adducts to identify human health risk from exposure to hazardous environmental pollutants: The increasing role of mass spectrometry in assessing biologically effective doses of genotoxic carcinogens

Analysis of DNA-phosphate adducts in vitro using miniaturized LC-ESI-MS/MS and column switching: Phosphotriesters and alkyl cobalamins

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