PMID: 2490568Jan 1, 1989Paper

Bio-analysis and preliminary pharmacokinetics of the experimental antitumour drug LL-D49194 alpha 1

Journal of Pharmaceutical and Biomedical Analysis
W J UnderbergJ H Beijnen

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.

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