Instruments are calibrated with substances of known relative molecular mass and very accurate mass
measurements can be made with this type of analyser. Sensitivity is very high and there is virtually no
upper limit to the working mass range. The performance of TOF instruments can be improved further
by the incorporation of an electrostatic reflector (reflectron) which ensures that all ions of identical
mass reach the detector simultaneously by correcting for any differences in their kinetic energies.
Tandem Mass Spectrometry
Instruments with two or more analysers have been developed to enable the further fragmentation and
study of selected ions entering the first analyser. The technique, known as tandem mass spectrometry,
or MS/MS, involves secondary fragmentation processes, usually induced by collisions with molecules
of an inert gas contained in a collision cell and described as collision-induced dissociation (CID). The
collision cell is positioned between two analysers which can be magnetic, electrostatic, quadrupole or
time-of-flight, but a triple quadrupole system (QQQ), in which the middle quadrupole acts as the
collision cell by applying only an RF signal, is a common configuration.
Recycling of ions through the system or adding more analysers and reaction zones extends the process,
which is then described as (MS)n. Three possible scanning modes of a QQQ system are shown in Figure
9.52(a), where MS 1 and MS 2 are the first and third analysers respectively.
(1) Product ion or fragment ion scan. An ion selected by MS 1 and known as a precursor ion is
subjected to CID in the middle quadrupole to give product ions which are analysed by MS 2.
(2) Precursor ion scan. A product ion is selected by MS 2 and a scan by MS 1 reveals which precursor
ions give rise to the selected product ion.
(3) Neutral loss scan. A neutral fragment is selected and both MS 1 and MS 2 are scanned simultaneously
but with a mass difference, or offset, between them equal to the mass of the neutral fragment being
studied. For example, if, during CID in the middle quadrupole, C 2 H 4 (mass 28) or H 2 O (mass 18)
molecules are lost from a fragment ion passing through MS 1 , then the MS 2 scan will be set to lag behind
the MS 1 scan by either 28 or 18 mass units. This will reveal which precursor ion leads to a particular
product ion by the specified neutral loss of 28 or 18 mass units. MS/MS and (MS)n are finding
considerable use, especially in HpLC-MS instruments, in establishing the exact configuration of
complex molecules.
Figure 9.52(b) demonstrates the value of MS/MS in studying fragmentation pathways. The EI spectrum
of 1,4-t-butylphenol includes a loss of mass 43 to give a fragment ion of mass 107. This could occur in
one step by the loss of C 3 H 7 (43) or by the loss of CH 3 (15) followed by a neutral loss of either CO or
C 2 H 4 (both 28). By selecting m/z 135 as the precursor ion, it