HYBRID TANDEM MASS SPECTROl\1:ETRY

The development of hybrid sector/quadrupole instruments for tanuc,m mass spectrom­ etry is described. The operational modes of these instruments are illustrated by MS /MS and MS/MS/MS analyses of peptides, xenobiotic metabolites and other compounds of biological impor­ tance. The versatility of operation (with respect to scan modes and the conditions utilized for collision­ ally activated decomposition) is a particular advantage of hybrid instruments. 1. Origins And Development Of Hybrid Instruments A hybrid mass spectrometer can be defined as a serial connection of two or more ion analyzers, each of which is based on different separation principles. Using this definition, we may regard the familiar double-focussIng instruments as representing one of the earliest hybrid designs. These instruments consist of a magnetic sector (B) which separates ions according to their momentum/charge ratio, and an electric sector (E), which separates according to kinetic energy/charge ratio. Appropriate geometries combining the two separation devices (either the electric sector first, magnet second, so-called EB, or BE) achieve double-focussing, and hence improved resolution, and also permit the establishment of connectivities between precursor and product ions. Two approaches are possible. With either the EB or BE configu­ rations, decompositions occurring in the first field-free region (FFR1, following the ion source) may be detected by linked scanning of Band E (1). BE instruments may be used to study the decompositions of precursor ions, selected by B, in the second field-free region (FFR2, between B and E); product ions are scanned by using E to give the mass-analyzed ion kinetic energy spectrum (MIKES) (2, 3). The limitations for the study of precursor/product ion relationships arise from the achievable reso­ lution of precursor or product ions. Scanning of FFRI decompositions is done with poor effective resolution of precursor ions whereas MIKES analyses have poor ef­ fective mass resolution of product ions. The simultaneous achievement of unit res­ olution or better of both precursor and product ions requires a tandem MS instru­ ment incorporating additional separation devices. In principle, any of the well known types of mass spectrometers can be connected in series to form tandem hybrid mass spectrometers. These include magnetic and electric sectors, quadrupole mass filters (Q), quadrupole ion traps, ion cyclotron res- 29