Determination of N-7-[2H3]methyl guanine in rat urine by gas chromatography-mass spectrometry following administration of trideuteromethylating agents or precursors |
| |
Authors: | D E Shuker E Bailey S M Gorf J Lamb P B Farmer |
| |
Institution: | MRC Toxicology Unit, Medical Research Council Laboratories, Woodmansterne Road, Carshalton, Surrey SM5 4EF, England |
| |
Abstract: | A gas chromatographic-mass spectrometric method has been developed for the determination of N-7-2H3]methyl guanine in urine in the presence of large natural levels of N-7-methyl guanine. Urine is fractionated on heptanesulfonic acid-treated C-18 Sep-pak cartridges, followed by derivatization to give a volatile N-heptafluorobutyryl-O6-2,3,4,5, 6-pentafluorobenzyl derivative which is separated on an SE52 fused silica capillary column. Using N-7-ethyl guanine as an internal standard, the total amount of N-7-methyl guanine is determined by gas chromatography-flame ionization detection. The percentage of N-7-2H3]methyl guanine is then measured by gas chromatography-mass spectrometry, enabling the amount of deuterated base to be determined. Preliminary experiments with 2H3]methyl methanesulfonate in rats showed measurable excretion of N-7-2H3]methyl guanine. 4-(Di2H3]methylamino)antipyrine alone gave no detectable amount of alkylated base, but coadministration of nitrite resulted in excretion of deuterated N-7-methyl guanine. |
| |
Keywords: | methylated bases 7-methyl guanine deuterium labeling alkylating agents gas chromatography mass spectrometry |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|