Profiling B-Type Natriuretic Peptide Cleavage Peptidoforms in Human Plasma by Capillary Electrophoresis with Electrospray Ionization Mass Spectrometry

J Proteome Res. 2017 Dec 1;16(12):4515-4522. doi: 10.1021/acs.jproteome.7b00482. Epub 2017 Oct 2.


B-type Natriuretic Peptide (BNP) is a biologically active circulating hormone. Plasma concentrations of BNP are routinely used in the diagnosis of heart failure, and the intravenous infusion of recombinant BNP can be used for heart failure treatment. Like many bioactive polypeptides, multiple plasma enzymes are known to cleave circulating BNP, and as part of the CVD-B/D-HPP mandate, we sought to develop a technique capable of profiling these catabolic processes in plasma. We used a neutral-coated capillary electrophoresis-electrospray ionization (CESI) separation system coupled with high-resolution mass spectrometry to profile the proteolysis of exogenous recombinant BNP1-32 in plasma. Our method utilizes electrokinetic injection of minimally processed plasma samples to simultaneously monitor the dynamic generation and breakdown of at least five BNP peptidoforms in plasma. By integrating multisegment injection, our method can produce a multipoint BNP proteolytic profile for one sample within an hour. We envision applying this method to assess the potential relation between plasma-based BNP proteolysis and heart failure as well as a means of monitoring BNP bioavailability after therapeutic infusion.

Keywords: CESI 8000; brain natriuretic peptide; capillary electrophoresis; mass spectrometry; multisegment injection; neutral capillary; peptidoforms; proteolysis profile.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Electrophoresis, Capillary
  • Heart Failure / metabolism
  • Humans
  • Natriuretic Peptide, Brain / blood
  • Natriuretic Peptide, Brain / metabolism*
  • Proteolysis*
  • Spectrometry, Mass, Electrospray Ionization


  • Natriuretic Peptide, Brain