Analysis of Anticancer Drugs and their Metabolites by Mass Spectrometry

Ian A. Blair; Anita Tilve

Abstract

There is an increasing awareness that the metabolites of anticancer drugs can contribute to the pharmacodynamic effects that are observed, which has stimulated a much greater emphasis on metabolic and pharmacokinetic issues. This has coincided with the development of electrospray and related atmospheric pressure ionization mass spectrometry techniques such as ionspray (nebulizer assisted electrospray), turboionspray (heated nebulizer assisted electrospray) and atmospheric pressure chemical ionization (nebulization coupled with corona discharge). The combination of collision induced dissociation and tandem mass spectrometry coupled with a soft ionization process that produces abundant molecular species provides very powerful methodology for the trace analysis of drugs and their metabolites. The present review has emphasized the more rigorous quantitative applications that have appeared in the literature over the last five years. It is evident that modern techniques of liquid chromatography tandem mass spectrometry coupled with stable isotope dilution methodology have had a profound effect on our ability to analyze anticancer drugs and their metabolites. As new drugs emerge into the clinic, this methodology will clearly be the method of choice, particularly when many samples have to be analyzed over a short time. This approach was beautifully demonstrated in the study of the novel signal transduction inhibitor, Gleevec where thousands of clinical samples were analyzed for drug and metabolites over a relatively short period of time. The need to analyze anticancer drugs and their metabolites with such prompt turn around times has stimulated even more rapid approaches to analysis using roboticbased purification methodology and short LC chromatographic run times.

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