One- and Multidimensional Liquid Chromatographic and Mass Spectrometric Strategies for the Quality Control of Natural, Synthetic and Therapeutic Peptides

Abstract

The demand for therapeutic and synthetic peptides has been steadily increasing in the past decade. They occupy an interesting chemical space between traditional small molecule drugs and large ones such as proteins and are predominantly accessible through the synthetic route according to Merrifield, which is inherently prone to various peptide related impurities that pose a challenge for their quality control. The current state-of-the-art methodology is limited to RPLC (0.1 % TFA) hyphenated to UV detection, where co-eluting and chiral impurities likely remain unrevealed. Hence, sophisticated analytical strategies were developed to recognize various impurities utilizing both chemo- and enantioselective multidimensional liquid chromatographic approaches combined with high resolution mass spectrometry and various complementary detection methods.