Mass spectrometry in high throughput analysis

The rapid growth of high throughput chemistry has created a need for faster, more accurate, and more sensitive analytical techniques capable of large-scale screening. Numerous improvements in speed, sensitivity and accuracy, together with innovations in both automation and quantitation, place mass spectrometry among the most powerful analytical techniques available today. There are now many analyzer options for high throughput analysis of compounds as well as multiple ionization techniques that have a much greater range of compatible compounds than were available even five years ago. Quantitative ESI-MS has been shown to be an effective assay for the identification of inhibitor activity in a combinatorial library, namely potent nucleotide inhibitors of a galactosyltransferase. Clearly, this approach can be applied to a variety of different reaction systems. A combinatorial extraction method in conjunction with an automated MALDI mass spectrometric procedure was also used to optimize the clinical analysis of the immunosuppressant drug CsA from whole blood. MALDI-based assays are versatile tools for the high-throughput genotyping of SNPs and other point mutations in human DNA. In addition, MALDI was shown to be an effective method for the direct analysis of resin-bound compounds (without chemical cleavage from the resin), an ideal technique for the identification/characterization of combinatorial compounds synthesized on solid supports. Furthermore, DIOS has recently been developed as an effective small molecule and proteomics tool and offers the potential of high throughput analysis of a wide variety of compounds. Overall, the strength of mass spectrometry lies in such versatility, making it a powerful analytical technique with which to characterize the diversity of compounds found in modern high throughput chemistry.