Improving limits of detection for B-type natriuretic peptide using PC-IDMS: An application of the ALiPHAT strategy

Christopher M. Shuford, Daniel L. Comins, Jerry L. Whitten, John C Jr. Burnett, David C. Muddiman

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Hydrophobic tagging of biomolecules has been reported by our group and others to increase their ionization efficiency during electrospray ionization and facilitate their detection by mass spectrometry. As such, hydrophobic tagging should provide a viable method for augmenting MS-based quantification of low abundance proteins by decreasing their detection limits. Herein we have evaluated two commercial alkylation reagents and several newly synthesized hydrophobic alkylation reagents for their utility in quantifying B-type Natriuretic Peptide, a low abundance cardiac biomarker, by protein cleavage isotope dilution mass spectrometry. For the cysteine containing tryptic peptide evaluated, a ∼3.5-fold decrease in the detection limit was observed for the best performing hydrophobic reagent, 2-iodo-N-octylacetamide, relative to the commonly used alkylation reagent, iodoacetamide. Additionally, we have evaluated the use of nonpolar surface areas as a metric for assessing the effectiveness of the alkylation reagents in improving ESI response.

Original languageEnglish (US)
Pages (from-to)36-41
Number of pages6
JournalAnalyst
Volume135
Issue number1
DOIs
StatePublished - 2010

Fingerprint

Brain Natriuretic Peptide
Alkylation
peptide
Limit of Detection
tagging
ionization
mass spectrometry
Mass spectrometry
protein
Mass Spectrometry
Proteins
Electrospray ionization
cleavage
biomarker
Biomolecules
dilution
Biomarkers
Iodoacetamide
surface area
isotope

ASJC Scopus subject areas

  • Analytical Chemistry
  • Spectroscopy
  • Electrochemistry
  • Biochemistry
  • Environmental Chemistry

Cite this

Improving limits of detection for B-type natriuretic peptide using PC-IDMS : An application of the ALiPHAT strategy. / Shuford, Christopher M.; Comins, Daniel L.; Whitten, Jerry L.; Burnett, John C Jr.; Muddiman, David C.

In: Analyst, Vol. 135, No. 1, 2010, p. 36-41.

Research output: Contribution to journalArticle

Shuford, Christopher M. ; Comins, Daniel L. ; Whitten, Jerry L. ; Burnett, John C Jr. ; Muddiman, David C. / Improving limits of detection for B-type natriuretic peptide using PC-IDMS : An application of the ALiPHAT strategy. In: Analyst. 2010 ; Vol. 135, No. 1. pp. 36-41.
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