Differentiation of enantiomeric drugs by iodo-substituted L-amino acid references under electrospray ionization mass spectrometric conditions
Article first published online: 26 APR 2012
Copyright © 2012 John Wiley & Sons, Ltd.
Rapid Communications in Mass Spectrometry
Volume 26, Issue 11, pages 1385–1391, 15 June 2012
How to Cite
Karthikraj, R., Prabhakar, S. and Vairamani, M. (2012), Differentiation of enantiomeric drugs by iodo-substituted L-amino acid references under electrospray ionization mass spectrometric conditions. Rapid Commun. Mass Spectrom., 26: 1385–1391. doi: 10.1002/rcm.6237
- Issue published online: 17 APR 2012
- Article first published online: 26 APR 2012
- Manuscript Revised: 23 MAR 2012
- Manuscript Accepted: 23 MAR 2012
- Manuscript Received: 27 DEC 2011
In chiral differentiation by mass spectrometry, use of a single reference that differentiates various classes of compounds including drugs is ideal, but so far there are no such reports in the literature. We have successfully used iodo-substituted amino acids for the chiral differentiation of ten enantiomeric pairs of drugs.
To achieve the chiral differentiation, the trimeric Cu complex ion consisting of two chiral reference molecules and an analyte molecule was generated under positive ion electrospray ionization (ESI) conditions and subsequently subjected for collision- induced dissociation (CID) experiments using an LCQ ion trap mass spectrometer. The spectra were recorded under identical experimental conditions for both the enantiomers, and were averages of 30 scans. Cooks' kinetic method and chiral recognition ratio method (CR method) were used to arrive at the Rchiral/CR values, respectively.
The Rchiral or CR values of the studied drugs are higher for 3,5-diiodo-L-tyrosine as the reference, than for 4-iodo-L-phenylalanine, except for isoproterenol and atenolol. Both the references show the same selectivity (R- or S-selectivity) towards all the studied drugs. With 3,5-diiodo-L-tyrosine as the reference, an Rchiral value of 12.75 is obtained for DOPA and this is the highest reported value in the literature till now. The suitability of the current method in measuring enantiomeric excess is also demonstrated for DOPA.
The use of 4-iodo-L-phenylalanine or 3,5-diiodo-L-tyrosine as a chiral reference for the chiral differentiation of ten enantiomeric pairs of pharmaceutically important drugs has been demonstrated. The chiral differentiation of pregabalin, tenofovir and pramipexole is reported for the first time. This study shows that it is possible to develop a single chiral reference compound for the differentiation of a group of chiral drugs having some similarities. Copyright © 2012 John Wiley & Sons, Ltd.