Mass tandem

The elucidation of acetogenin structures is rather difficult and requires, besides classical methods such as UV, IR, proton and carbon NMR and mass spectrometry, some innovative mass strategies such as mass-tandem or collision-induced-dissociation (CID) of [M+Li]+ ions using linked... 

Figure 5. Mapping of protein polymorphisms by mass spectrometry. A Major Urinary Protein from Mus spretus was purified and Lys-C digestion fragments were mass measured by MALDl-ToF mass spectrometry. Four of the peptides had the same masses as the equivalent protein from Mus domesticus. However, for two of the remainder, of novel mass, tandem mass spectrometry led to the identification of an amino acid change that was consistent with the new peptide mass. (J is used to define leucine or isoleucine, which cannot be distinguished by this type of mass spectrometry).

Magnetic sectors can be used on their own, or in conjunction with energy analysers to fomi a tandem mass spectrometer. The unique features of the reverse geometry instrument are presented from this point. 

A single magnetic sector can be used as a mass filter for other apparatus. However, much more infonnation of the simple mass spectrum of a species can be obtained using the tandem mass spectrometer. 

Another approach to mass analysis is based on stable ion trajectories in quadnipole fields. The two most prominent members of this family of mass spectrometers are the quadnipole mass filter and the quadnipole ion trap. Quadnipole mass filters are one of the most connnon mass spectrometers, being extensively used as detectors in analytical instnunents, especially gas clnomatographs. The quadnipole ion trap (which also goes by the name quadnipole ion store, QUISTOR , Paul trap, or just ion trap) is fairly new to the physical chemistry laboratory. Its early development was due to its use as an inexpensive alternative to tandem magnetic sector and quadnipole filter instnunents for analytical analysis. It has, however, staned to be used more in die chemical physics and physical chemistry domains, and so it will be described in some detail in this section. 

Aside from the smgle mass filter, the most connnon configuration for quadnipole mass spectrometers is the triple-quadnipole instrument. This is the simplest tandem mass spectrometer using quadnipole mass filters. Typically, the... 

One of the prineiple uses of the ion trap is as a tandem-in-time mass speetrometer. Ions with a partieular m/z ratio fomied in the ion trap, or mjeeted into the trap from an external soiiree, ean be isolated by resonantly ejeeting all other... 

This is one of the newer books covering tandem spectrometry and is a useful resource for the beginner and experienced mass... 

An AutoSpec-TOF mass spectrometer has a magnetic sector and an electron multiplier ion detector for carrying out one type of mass spectrometry plus a TOF analyzer with a microchannel plate multipoint ion collector for another type of mass spectrometry. Either analyzer can be used separately, or the two can be run in tandem (Figure 20.4). 

Until 1981, mass spectrometry was limited, generally, to the analysis of volatile, relatively low-molecular-mass samples and was difficult to apply to nonvolatile peptides and proteins without first cutting them chemically into smaller volatile segments. During the past decade, the situation has changed radically with the advent of new ionization techniques and the development of tandem mass spectrometry. Now, the mass spectrometer has a well-deserved place in any laboratory interested in the analysis of peptides and proteins. 

Tandem mass spectrometers most commonly used for MS/MS smdies include the following analyzer combinations, although many others are possible ... 

However, interpretation of, or even obtaining, the mass spectrum of a peptide can be difficult, and many techniques have been introduced to overcome such difficulties. These techniques include modifying the side chains in the peptide and protecting the N- and C-terminals by special groups. Despite many advances made by these approaches, it is not always easy to read the sequence from the mass spectrum because some amide bond cleavages are less easy than others and give little information. To overcome this problem, tandem mass spectrometry has been applied to this dry approach to peptide sequencing with considerable success. Further, electrospray ionization has been used to determine the molecular masses of proteins and peptides with unprecedented accuracy. 

Tandem mass spectrometry (MS/MS) produces precise structural or sequence information by selective and specific induced fragmentation on samples up to several thousand Daltons. For samples of greater molecular mass than this, an enzyme digest will usually produce several peptides of molecular mass suitable for sequencing by mass spectrometry. The smaller sequences can be used to deduce the sequence of the whole protein. 

MS/MS. two mass spectrometers used in tandem (sometimes written as MS2)... 

Busch, K.L., Glish, G.L., and McLuckey, S.A., Mass Spectrometry/Mass Spectrometry Techniques and Applications of Tandem Mass Spectrometry, VCH, New York, 1988. 

Kinter, M. and Sherman, N.E., Protein Sequencing and Identification Using Tandem Mass Spectrometry, Wiley, Chichester, U.K., 2000. 

McFadden, W.H., Techniques of Combined Gas Chromatography/Mass Spectrometry, Wiley, New York, 1973. McLafferty, F.W., Tandem Mass Spectrometry, Wiley, New York, 1983. 

E. W. McLafferty, ed.. Tandem Mass Spectromety,]ohn Wiley Sons, Inc., New York, 1983. 

Multidimensional or hyphenated instmments employ two or more analytical instmmental techniques, either sequentially, or in parallel. Hence, one can have multidimensional separations, eg, hplc/gc, identifications, ms/ms, or separations/identifications, such as gc/ms (see CHROMATOGRAPHY Mass spectrometry). The purpose of interfacing two or more analytical instmments is to increase the analytical information while reducing data acquisition time. For example, in tandem-mass spectrometry (ms/ms) (17,18), the first mass spectrometer appHes soft ionization to separate the mixture of choice into molecular ions the second mass spectrometer obtains the mass spectmm of each ion. 

Tandem mass spectrometry or ms/ms was first introduced in the 1970s and gained rapid acceptance in the analytical community. The technique has been used for stmcture elucidation of unknowns (26) and has the abiUty to provide sensitive and selective analysis of complex mixtures with minimal sample clean-up (27). Developments in the mid-1980s advancing the popularity of ms/ms included the availabiUty of powerhil data systems capable of controlling the ms/ms experiment and the viabiUty of soft ionisation techniques which essentially yield only molecular ion species. 

The most common modes of operation for ms/ms systems include daughter scan, parent ion scan, neutral loss scan, and selected reaction monitoring. The mode chosen depends on the information required. Stmctural identification is generally obtained using daughter or parent ion scan. The mass analyzers commonly used in tandem systems include quadmpole, magnetic-sector, electric-sector, time-of-flight, and ion cyclotron resonance. Some instmments add a third analyzer such as the triple quadmpole ms (27). 

The main advantages of the ms/ms systems are related to the sensitivity and selectivity they provide. Two mass analyzers in tandem significantly enhance selectivity. Thus samples in very complex matrices can be characterized quickly with Htde or no sample clean-up. Direct introduction of samples such as coca leaves or urine into an ms or even a gc/lc/ms system requires a clean-up step that is not needed in tandem mass spectrometry (28,29). Adding the sensitivity of the electron multiplier to this type of selectivity makes ms/ms a powerhil analytical tool, indeed. It should be noted that introduction of very complex materials increases the frequency of ion source cleaning compared to single-stage instmments where sample clean-up is done first. 

The liquid chromatography - tandem mass spectrometry (LC/MS/MS) technique was proposed for the determination of corticosteroids in plasma and cerebrospinal fluid (CSF, liquor) of children with leucosis. Preliminai y sample prepai ation included the sedimentation of proteins, spinning and solid-phase extraction. MS detection was performed by scanning selected ions, with three chai acteristic ions for every corticosteroids. The limit of detection was found 80 pg/ml of plasma. 

FIGURE 5.24 Tandem mass spectrometry, (a) Configuration used in tandem MS. 

An on-line chromatography/atmospheric pressure chemical ionization tandem mass spectrometry (LC-APCI/MS/MS) methods was developed for rapid screen of pharmacokinetics of different drugs, including 5 (98RCM1216). The electron impact mass spectrum of 5 and ethyl 9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7Ff-pyrido[l,2,3- fe]-l,4-benzoxazine-6-carboxylate was reported (97MI28). Electron impact/Fourier transform... 

J. Cai and J. Henion, Quantitative multi-residue determination of /3-agonists in bovine urine using on-line immunoaffinity extr action-coupled column packed capillary liquid cliromatogr aphy-tandem mass spectr ometry , 7. Chromatogr. 691 357-370 (1997). 

P. O. Edlund, E. Bowers and J. Henion, Detemination of methandrostenolone and its metabolites in equine plasma and urine by coupled-column liquid cliromatography with ulti aviolet detection and confimation by tandem mass spectrometiy , 7. Chromatogr. 487 341-356(1989). 

K. Ki onkvist, M. Gustavsson, A.-K. Wendel and H. Jaegfeldt, Automated sample preparation foi the determination of budesonide in plasma samples by liquid chi omatography and tandem mass specti ometi y , 7. Chromatogr. A 823 401-409 (1998). 

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