title: A sensitive high-performance liquid chromatographic assay for melphalan and its hydrolysis products in blood and plasma.
abstract: A sensitive high-performance liquid chromatographic assay has been developed for the measurement of the alkylating cytostatic drug melphalan (4-[bis(2-chloroethyl)amino]-L-phenyl-alanine, or L-phenylalanine-mustard, L-PAM) and its two hydrolysis products, monohydroxy melphalan (MOH) and dihydroxy melphalan (DOH). A reversed-phase phenyl column and a mobile phase consisting of acetonitrile/citrate buffer made possible an isocratic separation and quantification. N,N-[bis(2-hydroxy-ethyl)]toluidine has been synthesized as an internal standard structurally related to DOH. A new, accurate "kinetic" calibration procedure enabled us to determine even the concentration of the unstable MOH. The lower limit of quantification was 30 ng/ml for L-PAM and 20 ng/ml for both DOH and MOH with fluorescence detection. The use of this method is illustrated by some pharmacokinetic data in systemic and locoregional melphalan therapy.
authors.affiliation: Department of Internal Medicine, University of Bonn, Federal Republic of Germany.
authors.forename: H K
authors.initials: HK
authors.lastname: Osterheld
authors.forename: E
authors.initials: E
authors.lastname: Musch
authors.forename: G E
authors.initials: GE
authors.lastname: von Unruh
authors.forename: U
authors.initials: U
authors.lastname: Loos
authors.forename: H
authors.initials: H
authors.lastname: Rauschecker
authors.forename: B J
authors.initials: BJ
authors.lastname: Mühlenbruch
mesh_terms: D002138:Calibration; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D006868:Hydrolysis; D008558:Melphalan / Q000097:blood* / Q000493:pharmacokinetics; D011237:Predictive Value of Tests; D011786:Quality Control
chemical_list: D008558:Melphalan