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First results of a quantitative study of DNA adducts of melphalan in the rat by isotope dilution mass spectrometry using capillary liquid chromatography coupled to electrospray tandem mass spectrometry
Author(s) -
Van den Driessche Bart,
Esmans Eddy L.,
Van der Linden Annemie,
Van Dongen Walter,
Schaerlaken Evi,
Lemière Filip,
Witters Erwin,
Berneman Zwi
Publication year - 2005
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.2018
Subject(s) - chemistry , chromatography , isotope dilution , melphalan , mass spectrometry , adduct , tandem mass spectrometry , dna adduct , liquid chromatography–mass spectrometry , transplantation , organic chemistry , medicine , surgery
Abstract Rats were intravenously injected with a single high dose (10 mg/kg) of the alkylating agent melphalan in order to study DNA‐adduct formation. Quantitation of a dGuo‐melphalan adduct was done by isotope dilution mass spectrometry using capillary liquid chromatography/mass spectrometry (LC/MS) and [ 15 N 5 ]‐labeled dGuo‐melphalan as internal standard. DNA‐adduct levels were studied in bone marrow, liver and kidney. The instrumental detection limit of the method was determined to be 900 fg (S/N 3, pure standard). These first results clearly show a 10 times higher adduct level in bone marrow compared to kidney and a 6 times higher level compared to liver. More experiments will be necessary to gather more information on the pharmacokinetics of melphalan‐DNA adducts under in vivo conditions. Copyright © 2005 John Wiley & Sons, Ltd.