Hybrid Q-TOF

Traditional detectors (i.e., FID electron capture detector, BCD nitrogen-phosphorous detector, NPD) supply only retention data. However, in many cases this is not enough for proper identification of analytes. Application of GC coupled with an MS detector gives much more information (i.e., the mass spectmm of each compound). GC-MS is a well known and frequently used technique that combines the highly effective separation of GC with the high sensitivity and selectivity of MS. Moreover, improvements in analytical instruments based on different types of mass analyzers (ion trap, quadrupole, and TOF) and the development of hybrid Q-TOF has enhanced the analytical capabilities of modem hardware. Different kinds of mass spectrometers are presented in Table 14.2 [119]. 

Clauwaert et al. [70] compared the quantitative performance for 3,4-MDMA and related compoimds of an existing method based on fluorescence detection to an LC-ESI-MS method on a quadrapole-time-of-flight hybrid (Q-TOF) system. With nearly four decades (2-10,000 pg on-colunm), the linear dynamic range and the absolnte sensitivity of the LC-MS method was superior. 

Zhou and Johnston [55] reported protein characterization by capillary isoelectric focussing (CIEF) on-hne coupled to RPLC-MS. Direct coupling of CIEF to ESl-MS is limited by interferences by the ampholytes. Inserting RPLC in-between can help removing these interferences. CIEF is performed in combination with a microdialysis membrane-based cathodic cell to remove the ampholyte and to collect protein fractions by stop-and-go CIEF prior to transfer to a 5><0.3-pm-ID C,8 trapping colunm and RPLC separation on a 50><0.3-pm-ID C4 column. The separation is performed using an acetonitrile-water gradient (0.1% acetic acid). ESI-MS is performed on a quadrupole-TOF hybrid (Q-TOF) instrument. 

In early negative-ion ESI-MS studies, halogenated solvent additives were applied to reduce the risk of discharge formation (Ch. 6.3.2). The use of 1,1,1,3,3,3,-hexafluoro-2-propanol (HFIP) to the mobile phase was proposed for oligonucleotides [22]. This is for instance applied in the rapid characterization of synthetic oligonucleotides by microcapillary LC-MS on a quadrupole-time-of-flight hybrid (Q-TOF) instrument [20]. 

Garzotti, M. Rovatti, L. Hamdan, M. Coupling of a Supercritical Fluid Chromatography System to a Hybrid (Q-TOF 2) Mass Spectrometer On-line Accurate Mass Measurements, Rapid Commun. Mass Spectrom. 15, 1187-1190 (2001). 

Various forms of tandem mass spectroscopy (MS/MS) have also been used in the analysis of biomolecules. Such instruments consist of an ionisation source (ESI or MALDI or other) attached to a first mass analyser followed by a gas-phase collision cell. This collison cell further fragments the selected ions and feeds these ions to a second mass detector. The final mass spectrum represents a ladder of fragment ions. In the case of peptides the collision cell usually cleaves the peptides at the amide bond. The ladder of resulting peptides reveals the sequence directly [496]. Thus, tandem MS instruments, such as the triple quadrupole and ion-trap instruments have been routinely applied in LC-MS/MS or ESI-MS/MS for peptide sequencing and protein identification via database searching. New configurations, which have been moving into this area include the hybrid Q-TOF [498], the MALDI-TOF-TOF [499] and the Fourier transform ion cyclotron resonance instruments [500]. 

The very first microfluidic-MS applications have involved sample infusion analysis from chips with a flat spraying surface or with inserted ESI capillary emitters. These relatively simple devices were fabricated from glass or polymeric substrates and were interfaced to IT, TOP, or hybrid Q-TOF instruments, and sample infusion was accomplished by connecting syringe pumps, N2 cylinders, or external EOF pumping capillaries to the chip. Alternatively, infusion experiments have... 

High sensitivity. It was demonstrated that introduction of the TWIMS device does not compromise the intrinsic sensitivity of the hybrid Q-TOF instrument. 

Ease of use. Because the instrument is essentially a modified version of a successful hybrid Q-TOF, then interfaces to separation science components (under full computer control), data acquisition, data processing, and other conventional mass spectrometry experiments are already developed fully. 

Recently, an extremely powerful hybrid Q-TOF system has been introduced, based on a quadrupole analyser as the front-end and a TOF analyser as the back-end (Q-q ipTOF geometry). As a result of the orthogonal geometry of the quadrupole and TOF, the TOF analyser enables high-resolution operation and thus accurate mass determination (up to 5 ppm), which can be extremely useful in structure elucidation by MS-MS, e.g. in peptide sequencing and impurity profiling. 

The use of a smface as collision target was first demonstrated by Cooks et al. in a sector-type mass spectrometer by dissociation of CO-. These authors concluded that SID resulted in a fragmentation spectrum very similar to that of high-energy CID of the same species, and they highUghted experimental convenience as the major advantage of SID. Since this first implementation, SID has been demonstrated in a variety of mass spectrometers, including quadrupole, TOF, hybrid Q-TOF, and FT-lCR. " A crucial aspect of... 

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