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.
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.
Van den Driessche
Bart
B
Nucleoside Research and Mass Spectrometry Unit & Centre for Proteomics and Mass Spectrometry, Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium.
Esmans
Eddy L
EL
Van der Linden
Annemie
A
Van Dongen
Walter
W
Schaerlaken
Evi
E
Lemière
Filip
F
Witters
Erwin
E
Berneman
Zwi
Z
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*
D018906:Antineoplastic Agents, Alkylating; D018736:DNA Adducts; D009587:Nitrogen Isotopes; D008558:Melphalan