Optimized separation of β-blockers with multiple chiral centers using capillary electrochromatography–mass spectrometry☆

Abstract

This work focuses on the simultaneous analysis of β-blockers with multiple stereogenic centers using capillary electrochromatography–mass spectrometry (CEC–MS) with a vancomycin stationary phase. The critical mobile phase variables (composition of organic solvents, acid/base ratios) as well as column temperature and electric field strength, effecting enantioresolution and analysis time were first optimized sequentially. Next, to achieve global optimum a multivariate D-optimal design was used. Although multivariate approach did not improve enantioresolution any further, analysis time was significantly reduced. Under optimum CEC–MS conditions, all stereoisomers were resolved with resolution in the range 1.0−3.1 in less than 60 min with an average signal-to-noise (S/N) greater than 1000. The developed CEC–MS method has the potential to emerge as a screening method for analysis of multiple chiral compounds using a single protocol using the same column and mobile phase conditions, thus reducing the operation time and cost.

Theory and Practice of UHPLC and UHPLC–MS

“…The coupling of CEC with MS has also been demonstrated utilizing different ESI interfaces, e.g., sheathless (Warriner et al, 1998), coaxial sheath-flow (Desiderio and Fanali, 2000;Bragg et al, 2008), and liquid-junction (Lee et al, 1989;D'Orazio and Fanali, 2010). Among the interfaces used, the last one seems to be very promising because minimizing the drawbacks derived by the use of the high electric field applied, bubble formation, ion signal stability, and sensitivity.…”

Enantioselective capillary electrochromatography: Recent developments and new trends

“…This group continued method development with the same CSP for two b-blockers with multiple chiral centers, i.e. nadolol and labetalol [34]. An experimental design approach was used to optimize the simultaneous separation of these two compounds.…”

Untitled

“…Chiral resolution of optical isomers of diltiazem molecule have already been achieved using capillary zone electrophoresis 2 , electro kinetic chromatography 3 and by HPLC [4][5] . Biological activity of diltiazem as antihypertensive agent and against acute myocardial infection and cardiac arrest 6 has been studied.…”