Recent advances in mass spectrometry-based approaches for proteomics and biologics: Great contribution for developing therapeutic antibodies

Pharmacol Ther. 2018 May:185:147-154. doi: 10.1016/j.pharmthera.2017.12.007. Epub 2017 Dec 22.

Abstract

Since the turn of the century, mass spectrometry (MS) technologies have continued to improve dramatically, and advanced strategies that were impossible a decade ago are increasingly becoming available. The basic characteristics behind these advancements are MS resolution, quantitative accuracy, and information science for appropriate data processing. The spectral data from MS contain various types of information. The benefits of improving the resolution of MS data include accurate molecular structural-derived information, and as a result, we can obtain a refined biomolecular structure determination in a sequential and large-scale manner. Moreover, in MS data, not only accurate structural information but also the generated ion amount plays an important rule. This progress has greatly contributed a research field that captures biological events as a system by comprehensively tracing the various changes in biomolecular dynamics. The sequential changes of proteome expression in biological pathways are very essential, and the amounts of the changes often directly become the targets of drug discovery or indicators of clinical efficacy. To take this proteomic approach, it is necessary to separate the individual MS spectra derived from each biomolecule in the complexed biological samples. MS itself is not so infinite to perform the all peak separation, and we should consider improving the methods for sample processing and purification to make them suitable for injection into MS. The above-described characteristics can only be achieved using MS with any analytical instrument. Moreover, MS is expected to be applied and expand into many fields, not only basic life sciences but also forensic medicine, plant sciences, materials, and natural products. In this review, we focus on the technical fundamentals and future aspects of the strategies for accurate structural identification, structure-indicated quantitation, and on the challenges for pharmacokinetics of high-molecular-weight protein biopharmaceuticals.

Keywords: Bioanalysis; Mass spectrometry; Pharmacokinetics; Proteomics; Structure identification; Therapeutic drug monitoring; nSMOL.

Publication types

  • Review

MeSH terms

  • Biological Products* / chemistry
  • Biological Products* / therapeutic use
  • Humans
  • Mass Spectrometry*
  • Proteins / chemistry
  • Proteins / therapeutic use
  • Proteomics*

Substances

  • Biological Products
  • Proteins