Mass spectrometry future directions

The recent development and comparative application of modern separation techniques with regard to determination of alkylphosphonic acids and lewisite derivatives have been demonstrated. This report highlights advantages and shortcomings of GC equipped with mass spectrometry detector and HPLC as well as CE with UV-Vis detector. The comparison was made from the sampling point of view and separation/detection ability. The derivatization procedure for GC of main degradation products of nerve agents to determine in water samples was applied. Direct determination of lewisite derivatives by HPLC-UV was shown. Also optimization of indirect determination of alkylphosphonic acids in CE-UV was developed. Finally, the new instrumental development and future trends will be discussed. 

Laser desorption methods (such as LD-ITMS) are indicated as cost-saving real-time techniques for the near future. In a single laser shot, the LDI technique coupled with Fourier-transform mass spectrometry (FTMS) can provide detailed chemical information on the polymeric molecular structure, and is a tool for direct determination of additives and contaminants in polymers. This offers new analytical capabilities to solve problems in research, development, engineering, production, technical support, competitor product analysis, and defect analysis. Laser desorption techniques are limited to surface analysis and do not allow quantitation, but exhibit superior analyte selectivity. 

Tandem mass spectrometry (i.e., MS-MS) is another technique that has recently become popular for the direct analysis of individual molecular markers in complex organic mixtures [87,505,509,578 - 583]. This technique provides a rapid method for the direct analysis of specific classes of molecular markers in whole sample extracts. In this approach the system is set up to monitor the parent ions responsible for a specific daughter ion as described above and the distribution of parent ions obtained under these conditions should provide the same information as previously obtained by GC-MS [505, 582]. Even greater specificity can be achieved by a combination of GC-MS-MS [516,584]. In view of the complexity of COM samples and the need to detect the presence of individual organic compounds or classes of compounds, it would seem that MS-MS, especially coupled with GC, would be extremely valuable in future environmental organic geochemistry studies. 

So far, only the coupling and the cleavage reactions have been automated. Future developments might provide automated conversion of the liberated thiazolinone derivatives into phenylthiohydantoins and their automated identification. Alternatively, mass spectrometry which has as yet rarely been employed for identification may be applied directly to the thiazolinones dispensing altogether with the conversion step... 

As future direction, and the fact that mass spectrometry has evolved very rapidly in the last decade, other mass spectrometry based technologies such as ion mobility (Thalassinos et al., 2004 Clemmer et al., 2005) may play an important role in the screening of reactive metabolites. This separation stage is orthogonal to the LC and mass spectrometric separations and occurs on an intermediate timescale... 

Variable recovery is a principal cause of non-equivalence of data and there is no straightforward solution to this problem [26], Artificially made reference samples or pure compounds added to test material cannot be used for estimations of recovery of analytes. Direct speciation analysis from the solid sample [27] is not feasible at present, although analytical methods are appearing that could be useful in the future (X-ray absorption spectrometry, laser mass spectrometry, static secondary ion mass spectrometry). 

The results obtained with this first generation focal plane M.S.-EOID system as well as studies by Beynon and others at Purdue University (15) demonstrated the technical feasibility of such a system. Furthermore, these studies led the way to solutions for the variety of fundamental problems, which were encountered during the development and helped point out the directions towards future changes necessary on the road towards a commercially practical design for use of the concept in routine applications of mass-spectrometry. It became obvious that the vidicon based camera system wets not the best approach. Some of the reasons for this are (1) Loss of sensitivity due to light losses in the dissector and the transfer optics (2) cost of the image dissector (3) lower dynamic range and sensitivity, slower read-out rate, etc., of the vidicon compared to alternate devices. 

Frequently industrial hygiene analyses require the identification of unknown sample components. One of the most widely employed methods for this purpose is coupled gas chromatography/ mass spectrometry (GC/MS). With respect to interface with mass spectrometry, HPLC presently suffers a disadvantage in comparison to GC because instrumentation for routine application of HPLC/MS techniques is not available in many analytical chemistry laboratories (3). It is, however, anticipated that HPLC/MS systems will be more readily available in the future ( 5, 6, 1, 8). HPLC will then become an even more powerful analytical tool for use in occupational health chemistry. It is also important to note that conventional HPLC is presently adaptable to effective compound identification procedures other than direct mass spectrometry interface. These include relatively simple procedures for the recovery of sample components from column eluate as well as stop-flow techniques. Following recovery, a separated sample component may be subjected to, for example, direct probe mass spectrometry infra-red (IR), ultraviolet (UV), and visible spectrophotometry and fluorescence spectroscopy. The stopped flow technique may be used to obtain a fluorescence or a UV absorbance spectrum of a particular component as it elutes from the column. Such spectra can frequently be used to determine specific properties of the component for assistance in compound identification (9). 

Future Directions for Mass Spectrometry in Drug Discovery... 

Future routine uses of MALDI mass spectrometry for the detection of combinatorial library components could include techniques that enable the analytical chemist to directly analyze reaction products from beads without using prior cleavage reactions, as is shown in Fig. 7. This means that standard linker molecules would have to be designed in such a way that cleavage from the bead is obtained by the laser irradiation used for the ionization process as has been employed by Oda et al. and others (71,78) for the identification of peptides bound to a resin (72). 

III. FUTURE DIRECTIONS FOR THE APPLICATION OF MASS SPECTROMETRY IN COMBINATORIAL CHEMISTRY... 

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