Mass spectrometry synthesis quality control

Ball, R.W. and Packman, L.C. (1998) Matrix-assisted laser desorption ionization time-of-flight mass spectrometry as a rapid quality control method in oligonucleotide synthesis. 

LC/MS emerged as the method of choice for the quality control assessment to support parallel synthesis because the technique, unlike flow injection mass spectrometry, provides the added measure of purity (and quantity) of the compound under investigation. In addition, universal-like HPLC gradients (e.g., 10% to 90% acetonitrile in water in 5 minutes) have been found to satisfy the separation requirements for the vast majority of combinatorial and parallel synthesis libraries. Fast HPLC/MS has been found to serve as good surrogate to conventional HPLC for assessing library quantity and purity [34-37]. Fast HPLC/MS is simple in concept. It involves the use of short columns (typically 4.6 mm i.d. x 30 mm in length) operated at elevated flow rates (typically 3-5mL/min). 

As FIA-MS and liquid chromatography mass spectrometry (LC-MS) become more pervasive in the analysis of compound libraries, open-access instrumentation is increasingly used in HTOS laboratories as well as in support of general medicinal chemistry. These open-access systems are most often used for reaction monitoring and optimization, and in some cases, for library quality control and synthesis product purification. 

Edman degradation was originally developed for determination of the primary structure (i.e., amino acid sequence) of peptides and proteins. Sequence analysis is not regularly performed for quality control in routine peptide synthesis but is more often employed for problem solving. As described earlier in this chapter, efficient characterization of synthetic peptides can be readily obtained by a combination of RP-EDPLC and mass spectrometry. Amino acid analysis is also valuable if MS is not available. If an incorrect mass or a discrepancy in the amino acid composition is found, one obvious alternative is to resynthesize the peptide. But, in order to deduce the cause of a failed synthesis, additional analyses must be performed. Both Edman degradation and tandem MS can be used to obtain sequence information... 

Quality Control of Solid-Phase Synthesis by Mass Spectrometry... 

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