Tandem Mass Spectrometry: The Competitive Edge for Pharmacology

The notion of connecting two mass spectrometers to examine the chemistry of purified ion species was realized experimentally as early as 1954 (1), and ten years later instruments of this complexity had been constructed in five labora­ tories worldwide (2). The utility of collisions of fast-moving ionswith neutral target atoms to promote fragmentation was introduced by Jennings in 1968 (3). The analytical value of collisional activation and tandem mass spec­ trometry for components of mixtures received attention through the next decade (e. g. 4-6), and was demonstrated with a variety of instrumental configurations. The commercial availability around 1980 of tandem mass spectrometers based on three-sector analyzers and on three quadrupole an­ alyzers, and around 1985 of four-sector tandem instruments and of hybrids comprising two sectors and two quadrupole modules, rapidly increased the use of tandem (MSMS) techniques in analytical applications (7-14). Simply stated, these provide (a) a separation technique based on mass that removes chemical contamination (e. g. coelutants in HPLC peaks or matrix ions desorbed by fast atom bombardment) and separates components of mixtures, (b) reproducible and extensive fragmentation, and (c) increased selectivity through selected reaction monitoring. The selectivity and reliability provided by these powerful hyphenated instruments are compellingly relevant to prob­ lems in pharmacology. Applications of MSMS were included in about 100 papers in pharmacological journals in 1990.