Analysis of Brefeldin A in Plasma by Gas Chromatography with Electron Capture Detection

摘要: Abstract The National Cancer Institute (NCI) is pursuing preclinical development of Brefeldin A (BFA), a macrolide isolated from Penicillium brefeldianum , as an antitumor agent. BFA exhibits unique spectrum activity against the human tumor cell line panel that composes NCI′s recently established in vitro screen. specific method to assay compound biological fluids has been developed which and 1-eicosanol, added internal standard, are extracted plasma specimens with diethyl ether. residue afforded by evaporation organic solvent dried vacuo derivatized heptafluorobutyrylimidazole prior analysis capillary gas chromatography electron capture detection. Derivatization both secondary hydroxyl groups rapid quantitative, confirmed mass spectrometry. lowest concentration quantified acceptable reproducibility 50 μl 0.1 μg/ml, for 5.6% coefficient variation determined six standard curves assayed on separate days. Detector response positive deviation linearity samples concentrations greater than 2.5 μg/ml. shown application be suitable preliminary investigations pharmacokinetics mice. These studies reveal subject elimination mouse, levels declining apparent biphasic manner initial 33 0.2 μg/ml at 60 min after intravenous treatment 26.3mg/kg dose.