Separation mechanism of chiral impurities, ephedrine and pseudoephedrine, found in amphetamine-type substances using achiral modifiers in the gas phase

Anal Bioanal Chem. 2012 Nov;404(8):2407-16. doi: 10.1007/s00216-012-6365-0. Epub 2012 Sep 4.


A new mechanism is proposed that describes the gas-phase separation of chiral molecules found in amphetamine-type substances (ATS) by the use of high-resolution ion mobility spectrometry (IMS). Straight-chain achiral alcohols of increasing carbon chain length, from methanol to n-octanol, are used as drift gas modifiers in IMS to highlight the mechanism proposed for gas-phase separations of these chiral molecules. The results suggest the possibility of using these achiral modifiers to separate the chiral molecules (R,S) and (S,R)-ephedrine and (S,S) and (R,R)-pseudoephedrine which contain an internal hydroxyl group at the first chiral center and an amino group at the other chiral center. Ionization was achieved with an electrospray source, the ions were introduced into an IMS with a resolving power of 80, and the resulting ion clusters were characterized with a coupled quadrupole mass spectrometer detector. A complementary computational study conducted at the density functional B3LYP/6-31g level of theory for the electronic structure of the analyte-modifier clusters was also performed, and showed either "bridged" or "independent" binding. The combined experimental and simulation data support the proposed mechanism for gas-phase chiral separations using achiral modifiers in the gas phase, thus enhancing the potential to conduct fast chiral separations with relative ease and efficiency.

Publication types

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

MeSH terms

  • 1-Octanol / chemistry
  • Chemistry Techniques, Analytical
  • Chemistry, Pharmaceutical / methods*
  • Chemistry, Pharmaceutical / standards
  • Ephedrine / analysis*
  • Ephedrine / chemistry
  • Gases / chemistry
  • Mass Spectrometry
  • Pseudoephedrine / analysis*
  • Pseudoephedrine / chemistry
  • Stereoisomerism


  • Gases
  • Pseudoephedrine
  • Ephedrine
  • 1-Octanol