Abstract

This chapter describes operation and capabilities of liquid chromatography–mass spectrometry (LC–MS) instrumentation and explores how it can be best used for stable isotope tracer studies of drug disposition. The combined technique of LC–MS is widely recognized as the most powerful tool available for analysis with high sensitivity and specificity of low concentrations of drugs and their metabolites in biological matrices. The ability of LC–MS to distinguish and measure compounds labeled with stable isotopes with the same analytical prowess makes it the obvious choice when tracer studies with pharmaceuticals are considered. LC–MS interfaces are conveniently divided into two groups: (1) those that deliver the LC analytes to a conventional ion source for subsequent ionization, and (2) those that ionize the analytes and transmit the ions to the mass spectrometer. These are referred transport and ionization type interfaces, respectively. Transport interfaces deliver analytes from the High-performance liquid chromatography (HPLC) eluate to a conventional MS ion source where they are ionized and subsequently mass analyzed. They include the direct liquid introduction (DLI) and moving belt (MB) interface.

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