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 [ 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.