Liquid radiochromatographic techniques

Applications of radioisotopes to studies of ADME have been eomprehen-sively reviewed recently (Dalvie, 2000 Marathe et ah, 2004 Veltkamp, 1990). This chapter focuses on the recent advance in liquid radiochromatographic techniques and their application to metabolite detection and quantification in drug metabolism studies. In addition, the use of liquid radiochromatography coupled with mass spectrometry in metabolite profiling and structural elucidation is described. 

TABLE 10.1 Sensitivity of various liquid radiochromatographic techniques. 

Planar radiochromatography was the first widely used technique for separation and detection of radiolabeled metabolites (Veltkamp, 1990). The technique is very sensitive, fast, and has relatively low equipment and operating costs, however, due to low separation resolution and poor precision in quantification, it has largely been replaced by HPLC-based radiochromatographic techniques in the pharmaceutical industry. Online radio flow detection (RED) and off-line liquid scintillation counting (ESC) have been routinely used for analysis of radiolabeled metabolites for the last 15 years (Veltkamp, 1990). 

Liquid chromatography is routinely used for the quantitative analysis of a drug and its metabolites in radiolabeled in vitro metabolism experiments and in humans and animal ADME studies. Online radio-flow detection (RFD) and offline microplate scintillation counting (MSC) are the most commonly used radiochromatographic techniques in radiolabeled metabolite profiling and quantification (Boernsen et al., 2000 Nassar et ah, 2003 Bruin et al., 2006). LC/RFD is compatible with ESI mass spectrometry and provides high analytical speed and excellent separation resolution (Athersuch et al., 2008). 

---