Routine sensitive peptide mapping using LC/MS of therapeutic proteins produced by recombinant DNA technology.

At the Sixth International Conference on Methods in Protein Sequence Analysis held in Seattle, Washington, August 17-21, 1986, Frank Robey of the Food and Drug Administration (FDA) proposed a "wish list" of possible future techniques for the analysis of recombinant products. Included in this list was liquid chromatography (HPLC) in-line with mass spectrometry for peptide mapping. This wish has come true. In 1988, a new technique, electrospray ionization (ESI) of liquids with quadrupole mass analysis, became a major breakthrough in accurately measuring molecular weights of proteins up to 100,000 daltons or more. Now, using an affordable, simple, easy-to-use single-stage quadrupole mass spectrometer, peptide mapping is routine.