Theory and Instrumentation of Mass Spectrometry and its Application to Drug Metabolism

Abstract

Adsorption, distribution, metabolism, and excretion (ADME) studies demand that analytical methodologies used for analyses be sensitive, selective, accurate, precise, robust, and reproducible. Because of these requirements, liquid chromatography–mass spectrometry (LC-MS) has emerged as the preferred bioanalytical technique in ADME and drug metabolism and pharmacokinetic (DMPK) research. This article reviews the latest LC-MS instrumentation and techniques used in drug metabolism studies. For LC, the use and appropriateness of various chromatographic stationary phases as well as the use of ultraperformance (UP) LC and chip separations are discussed. The development of atmospheric pressure ionization (API) techniques, such as electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI), have made LC separation amenable to MS analysis. Typical mass analyzers used in drug discovery include the triple-stage quadrupole (TSQ), ion trap, and hybrid mass analyzers. In addition, the authors include information on the use of stable isotope dilution (SID) methodology, high-throughput techniques, and multivariate data analysis (MDA) as they pertain to drug metabolism studies. Keywords: LC-MS; drug metabolism; atmospheric pressure ionization; triple-stage quadrupole; ion-trap; stable isotope dilution; high-throughput analysis; multivariate data analysis