Drug Metabolism in Drug Design and Development Basic Concepts and Practice

trap, therefore, doubles the ion current. Because of these advantages one can
predict that in the not too distant future the LITs will replace the 3D ion traps.

11.2.3.5 Fourier Transform Mass Spectrometer (FTMS) Fourier transforma-
tion (FT) of time-dependent image from the detector tom/zintensity is utilized for
two types of mass spectrometers: ion cyclotron resonance (ICR) and Orbitrap.
FTICR mass spectrometers operate based on the ion cyclotron resonance
principle: ions in a magnetic field (B) move in circular orbits at frequencies (vc)
characteristic of theirm/zvalues as shown below (Marshall et al., 1998, 2002):

vc¼

zeB

2 pm

m=z¼

eB

2 pvc

An FTICRMS consists of three pairs of parallel plates arranged as a cube
that is used for trapping, excitation, and detection of ions. As shown in the
equation above, at a constant and uniform magnetic field (B) the cyclotron
frequency (vc) of an ion is inversely proportional to itsm/zvalue. Trapped ions
within an FTICRMS are detected by applying a frequency-sweep signal. When
the applied frequency becomes equal to the cyclotron frequency of ions at a
given m/z, the ions absorb energy and orbit at a larger radius. These
translationally excited ions move coherently between the receiver plates
generating image currents. The time-dependent image currents are subjected to
Fourier transformation that resolve the components of ion currents and
produce the mass spectrum. The FTICRMS can easily achieve a resolution of
100,000, thus providing accurate determination ofm/zvalues of unknown
metabolites more reliably than any other mass spectrometer available today.
FTICRMS systems are typically more expensive and possess a larger
laboratory footprint than other mass spectrometers.
Recently, a new high performance mass analyzer, called OrbitrapTM, has
been developed. The Orbitrap consists of an inner and an outer electrode,
which are shaped to create a quadro-logarithmic electrostatic potential. Ions
rotate about the inner electrode and oscillate harmonically along its axis (the
z-direction) with a frequency (vz) characteristic of theirm/zvalues:

vz¼

ffiffiffiffiffiffiffiffi

k

m=z

s

wherekis field curvature. These oscillations are observed using image current
detection and are transformed into mass spectra using fast Fourier transforms
(FFTs). High mass resolution (up to 150,000) and mass accuracy (2 ppm) have
been demonstrated (Day et al., 2005; Makarov, 2000; Hardman and Makarov,
2003).

328 APPLICATION OF LIQUID CHROMATOGRAPHY/MASS SPECTROMETRY