Chemical transformation/derivatization of O6-methyl- and O6-(hydroxyethyl)guanine for detection by GC-EC/MS.
Chiu-CS; Saha-M; Abushamaa-A; Giese-RW
Anal Chem 1993 Nov; 65(21):3071-3075
A technique for derivatizing O6-alkyl and O6-(hydroxyalkyl) guanines prior to detection by gas chromatography/electron capture/mass spectrometry was developed. The procedure was developed using O6- methylguanine (O6MeGua) and O6-(2'-hydroxyethyl)guanine (O6HOEtGua) as representative analytes. O6MeGua and O6OHEtGua were reacted with sodium-nitrite and tetrafluoroboric-acid to produce O6 substituted hypoxanthine derivatives. The hypoxanthine derivatives were subsequently reacted with pentafluorobenzyl-bromide to produce a series of pentafluorobenzyl ethers, pentafluorobenzyl-methyl ethers, pentafluorobenzyl-tert-butyl ethers, benzoyl-pentafluorobenzyl esters, and pivalyl-pentafluorobenzyl esters. The pentafluorobenzyl- tert-butyl ethers were selected as the best choice for quantitation by gas chromatography electron capture mass spectrometry (GC/EC/MS). The pentafluorobenzyl-tert-butyl ethers could be quantitated with detection limits of 1.16 and 1.24 picograms (pg). The detection limits for the pivalyl-pentafluorobenzyl derivatives were 1.27 and 1.31pg. The authors conclude that the procedure successfully converts O6meGua and O6OHETGua into derivatives that can be easily quantitated by GC/EC/MS.
NIOSH-Publication; NIOSH-Grant; Grants-other; DNA-adducts; Analytical-methods; Nucleosides; Chemical-reactions; Gas-chromatography; Mass-spectrometry
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Northeastern University, Boston, Massachusetts