Small Molecules Unmasked In Mass Spectrometry | Chemical & Engineering News
  • CORRECTION: This story was updated on Aug. 6, 2012, to eliminate using an incorrect word, "drug," to describe the natural product berberine.

Latest News
Web Date: July 30, 2012

Small Molecules Unmasked In Mass Spectrometry

Analysis: Deuterated matrix allows researchers to probe small-molecule pharmaceuticals with MALDI mass spec
Department: Science & Technology | Collection: Life Sciences
News Channels: Analytical SCENE, Biological SCENE
Keywords: MALDI, small molecules, pharmaceuticals, mass spectrometry

Mass spectrometry is useful for identifying many molecules, but one popular technique for probing biomolecules struggles to analyze small molecules. Now researchers have discovered that simply deuterating the matrix used in matrix-assisted laser desorption ionization (MALDI) mass spectrometry allows them to identify previously hidden small molecules, including neurotransmitters and pharmaceuticals (Anal. Chem., DOI: 10.1021/ac301498m).

Researchers are enthusiastic about MALDI’s ability to work directly with intact biological samples. In MALDI, researchers crystallize a sample inside a matrix material before they ionize it with a laser. The technique works well for molecules heavier than 600 daltons, but clusters of matrix molecules often mask the signal of smaller molecules.

Mohammadreza Shariatgorji, a postdoctoral researcher in Per Andrén’s medical mass spectrometry lab at Uppsala University, in Sweden, explains that researchers would like to detect small molecules including drugs, their metabolites, and biomolecules such as neurotransmitters.

Shariatgorji decided to move the matrix signals slightly so that the signals of small molecules known to be hidden by certain matrix clusters could be uncovered. He and his colleagues replaced four aromatic hydrogens with deuterium in a standard matrix material, α-cyano-4-hydroxycinnamic acid (CHCA). This shifted the matrix peaks by 4, 8, or 12 daltons for CHCA and for clusters of two or three CHCA molecules, respectively.

To demonstrate the technique, Shariatgorji and his colleagues used it on rat tissue samples to identify three small molecules: a natural product, berberine; a synthetic drug, amiloride; and a neurotransmitter, acetylcholine.

Andrén’s lab is already anticipating learning about disease with the technique: “It’s going to be really nice,” says Shariatgorji, “to trace the mechanism of acetylcholine-related diseases like Alzheimer’s and of aging in animal models.”

 
Chemical & Engineering News
ISSN 0009-2347
Copyright © American Chemical Society
Comments
Reza Akbari (August 2, 2012 5:36 AM)
Good luck Dear Dr. Shariat
I proud to you
Reza Akbari
PhD of Analytical Chemistry from babolsar, Iran

Leave A Comment

*Required to comment