title: Bio-analysis and preliminary pharmacokinetics of the experimental antitumour drug LL-D49194 alpha 1.
abstract: LL-D49194 alpha 1 is a recently discovered compound, produced by Streptomyces vinaceus-drappus. This micro-organism produces a number of antibiotics, all showing antibacterial and antitumour activity, of which LL-D49194 alpha 1 is one of the main compounds. The compounds' antitumour effectiveness has been proven in vitro and the drug is undergoing further tests. For the assay of the drug in plasma a high-performance liquid chromatographic (HPLC) system has been developed, preceded by a clean-up step. The drug is extracted from the biological matrix with ethyl acetate followed by direct HPLC analysis of the organic layer via an analytical RP8 column preceded by a guard column to retain endogenous plasma compounds. Detection of drug and metabolites was carried out by fluorescence with reference to a non-fluorescent internal standard detected by UV absorption. The detection limit was 1 ng ml-1 plasma (using 1 ml sample; signal-to-noise ratio, 3), i.e. 1 ng on column. The method has been utilized in a preliminary pharmacokinetic study in rat.
authors.affiliation: Department of Pharmaceutical Analysis, Faculty of Pharmacy, Utrecht University, The Netherlands.
authors.forename: W J
authors.initials: WJ
authors.lastname: Underberg
authors.forename: G A
authors.initials: GA
authors.lastname: Hofman
authors.forename: S C
authors.initials: SC
authors.lastname: Lubbers
authors.forename: O
authors.initials: O
authors.lastname: Bekers
authors.forename: W W
authors.initials: WW
authors.lastname: Ten Bokkel Huinink
authors.forename: J H
authors.initials: JH
authors.lastname: Beijnen
mesh_terms: D000617:Aminoglycosides; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D008954:Models, Biological; D051381:Rats; D012997:Solvents; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D012997:Solvents; C063725:LL-D49194 alpha1