High-performance liquid chromatographic methods for the determination of topoisomerase II inhibitors

Various methods for separating eleven different types of topoisornerase II (TOPO-2) inhibitors, including epipodophyllotoxins, anthracyclines, anthrac enediones, anthrapyrazoles, anthracenebishydrazones, indole derivatives, am ino-acridines, benzisoquinolinediones, isoflavones, bisdioxopiperazines and thiobarbituric. acids, are summarized. Proper sample preparation and stora ge is critical to the successful analysis of some TOPO-2 inhibitors due to difficulties associated with adsorption, instability and complex biological components. Solid-phase and liquid-liquid extractions are widely used to s eparate TOPO-2 inhibitors from biological samples, although simple deprotei nization followed by direct analysis of the supernatant is preferable to ex traction based on its speed and simplicity. High-performance liquid chromat ography (HPLC) is the favored method for the bioanalysis of TOPO-2 inhibito rs. UV or diode array detection is generally employed for early pharmacokin etic studies, while fluorescence or electrochemical detection is used more frequently for analytes with fluorescent or oxidative-reductive properties. For analyses requiring highly sensitive and/or specific detection, electro spray mass spectrometry (ESI-MS or ESI-MS-MS) provides a suitable alternati ve. A comprehensive compilation of the HPLC techniques currently used to se parate TOPO-2 inhibitors will aid the future development of analytical meth ods for new TOPO-2 inhibitors. (C) 2001 Elsevier Science B.V. All rights re served.