FTICR-mass spectrometry for high-resolution analysis in combinatorial chemistry

The diversity of compound collections required for finding lead structures in pharmaceutical research can be provided by means of combinatorial organic chemistry. The resultant enormous number of single compounds but also of compound mixtures represents a challenge for the analyst. With the introduction of Fourier transform ion cyclotron resonance mass spectrometry (FTICR‐MS or FT‐MS), a new and, as yet, not widespread mass spectrometric technique (a means of analysis of such compound libraries with a very high mass resolution) high mass accuracy and high sensitivity has become available. Moreover, in combination with electrospray ionization (ESI), not only high‐throughput measurements via flow‐injection analysis (FIA) but also coupling with separation techniques such as high‐performance liquid chromatography (HPLC) or capillary electrophoresis (CE) is possible. Structural verification by way of decomposing ions (MSn; n ≥ 2) using a variety of different dissociation techniques can be performed by FTICR‐MS. This is the first review specifically covering applications of FTICR‐MS in the field of combinatorial chemistry. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng (Comb Chem) 71:149–161, 2000/2001.