Capillary and Frontal Affinity Liquid Chromatography

To date, the vast majority of experiments in which liquid separation techniques have been coupled with MALDI have utilized off-line fraction collection. The availability of MALDI sample preparation robots has facilitated the preparation of hundreds of samples as discrete spots on the target plate in a short time frame. If the fraction collection is triggered by detection of a UV signal (or other analytical detector), then MS analysis can be focused only on the chromatographic regions which contain the most abundant analytes. In addition, fraction collection allows 

The wide variety of both numerous and diverse applications described in this chapter clearly demonstrates the utility and future potential of MALDI for both quahtative and quantitative characterization of LMM compounds. Many new instrumentation and sample preparation techniques are now available for automated and painless MALDI characterization. Arguably, sample preparation from complex mUieu such as blood still requires considerable attention and effort The sample dean-up procedures prior to MALDI analysis need not be more compUcated or lengthy than those conducted for ESl-MS analysis. Realistically, problems such as shot-to-shot and sample-to-sample reproducibility still exist, but can be overcome by the techniques discussed earlier. Other criticisms of quantitative MALDI such as poor sensitivity, limited linear range and imprecision (higher RSD) are primarily compound-dependent and have been significantly improved by instramental advancements. 

The somewhat surprising number and scope of publications on MALDI characterization of LMM compounds not only reinforces the utiUty and practical appU-cability of this technique, but also indicates the substantial efforts being made by several research groups. These efforts are transforming what might be pigeonholed as a high-molecular mass biomolecule-only analytical technique into a flexible analytical tool. 

The authors thank Steve Michael and Arkady Gusev for helpful reviews and discussion, and Mark Cole, Jason Gobey, Richard Knochenmuss, Dietrich Vohner, and Yinlong Guo who provided the figures for this chapter. 

AP-MALDl atmospheric pressure/matrix-assisted laser desorption/ionization 

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