title: 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.
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 [15N5]-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.
authors.affiliation: Nucleoside Research and Mass Spectrometry Unit & Centre for Proteomics and Mass Spectrometry, Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Van den Driessche
authors.forename: Eddy L
authors.initials: EL
authors.lastname: Esmans
authors.forename: Annemie
authors.initials: A
authors.lastname: Van der Linden
authors.forename: Walter
authors.initials: W
authors.lastname: Van Dongen
authors.forename: Evi
authors.initials: E
authors.lastname: Schaerlaken
authors.forename: Filip
authors.initials: F
authors.lastname: Lemière
authors.forename: Erwin
authors.initials: E
authors.lastname: Witters
authors.forename: Zwi
authors.initials: Z
authors.lastname: Berneman
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000032:analysis* / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods*; D018736:DNA Adducts / Q000032:analysis*; D008558:Melphalan / Q000032:analysis* / Q000737:chemistry; D009587:Nitrogen Isotopes / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D018736:DNA Adducts; D009587:Nitrogen Isotopes; D008558:Melphalan