Chapter 12 Identification and characterization of drug metabolites using stable isotope techniques

Abstract

This chapter discusses identification and characterization of drug metabolites using stable isotope techniques. A major use for stable isotopes in the identification and characterization of metabolites is to allow the analyst to readily identify the compound of interest in a complex biologic sample. By using a 1:1 mixture of labeled and unlabeled drugs, a characteristic ion cluster is produced that can readily be identified by mass spectrometry. This procedure, known as the “isotope cluster” technique, is widely used to simplify drug metabolite detection. Computer programs have been developed to identify potential drug metabolites by searching the entire chromatographic run, scan by scan, for the characteristic molecular ion cluster resulting from the isotopically enriched dosing solution. Isotope peak shift technique involves the determination of the metabolic site of the molecule based on loss of the stable label. A common application of the isotope peak shift technique is to use a stable isotope labeled derivatizing reagent in the identification and characterization of drug metabolites. The most common reagents used are deuterated trimethylsilyl (BSA or BSTFA) and acetic anhydride- d 6 .