Simultaneous Enantioseparation and Tandem UV−MS Detection of Eight β-Blockers in Micellar Electrokinetic Chromatography Using a Chiral Molecular Micelle

Abstract

The feasibility of using a new and more versatile polymeric chiral surfactant, i.e., poly(sodium N-undecenoxy carbonyl-L-leucinate (poly-L-SUCL) is investigated for simultaneous enantioseparation and detection of eight structurally similar beta-blockers with tandem UV and MS detection. Three optimization approaches, i.e., direct infusion-MS, capillary zone electrophoresis-MS, and chiral micellar electrokinetic chromatography-mass spectrometry (CMEKC-MS), were investigated to optimize sheath liquid parameters, spray chamber parameters, and CMEKC separation parameters for maximum sensitivity and chiral resolution. Compared to unpolymerized micelle of L-SUCL, the use of micelle polymer (i.e., poly-L-SUCL) provided significantly higher separation efficiency, lower separation current, and higher detection sensitivity for CMEKC-ESI-MS of beta-blockers. It was also observed that, unlike monomeric L-SUCL, polymeric L-SUCL provided enantioseparation of all beta-blockers even at the lowest surfactant concentration (i.e., 5 mM poly-L-SUCL). Under optimum CMEKC and ESI-MS conditions (15 mM poly-L-SUCL, 25 mM each of NH4OAc and TEA (pH 8.0); 80% (v/v) methanol sheath liquid containing 40 mM NH4OAc (pH 8.0); sheath liquid flow rate, 5.0 microL/min; drying gas flow rate, 5 L/min; drying gas temperature, 200 degrees C; nebulizing pressure, 6 psi (0.414 bar); capillary voltage, +2.5 kV; fragmentor voltage, 85 V), baseline enantioseparation of eight beta-blockers was achieved by tandem UV (in approximately 30 min) and MS (in approximately 60 min) detection. Calibration curves for all beta-blockers were linear in the range of 0.01-0.6 mM for both CMEKC-UV and CMEKC-MS methods, but the later method provided better concentration limit of detection with similar RSD for migration time and peak areas. The CMEKC-ESI-MS method appears suitable for use as a routine procedure for high-throughput separation of beta-blockers with high sensitivity.

Sensitive chiral analysis by CE: An update

“…On the other hand, polymeric surfactants (also called molecular micelles or micelle polymers) are very attractive as alternative pseudostationary phases to conventional micelles for the coupling of the MEKC separation mode with ESI-MS [44][45][46]. They provide several advantages over conventional micelles for this hyphenation [44,45]: (i) the covalent bonds between surfactant monomers are difficult to ionize in the electrospray resulting in less-background noise from surfactant monomers of low molecular weights in MEKC-MS applications, (ii) micellar solutions can be used at any polymer concentration due to zero CMC, consequently higher S/N are observed in MEKC-ESI-MS, and (iii) polymeric surfactants have lower surface activity and lower volatility, and are stable in the presence of a high content of organic modifier in the BGE, which also tends to enhance the ESI-MS intensity.…”

Review of aqueous chiral electrokinetic chromatography (EKC) with an emphasis on chiral microemulsion EKC

“…The difference between conventional micelles and micelle polymers can be seen in Fig. 1 where the resulting PSPs were used for MEKC-ESI-MS analyses [43].…”

“…The use of chiral polymeric micelles as chiral selectors in MEKC-ESI-MS, the second such study, was published in 2005 by Akbay et al [43]. Poly(sodium N-undecenoxycarbonyl-L-leucinate (poly-L-SUCL) was synthesized and employed for the concurrent testing of eight b-blockers.…”

Polymeric Sulfated Amino Acid Surfactants: A Class of Versatile Chiral Selectors for Micellar Electrokinetic Chromatography (MEKC) and MEKC-MS

“…39-41 Recently, our group conducted several studies with the chiral amino acid based polymeric surfactant which actually showed at least 5-14 fold better sensitivity in MEKC-MS compared to MEKC-UV method for chiral analysis. 31,[40][41] The pH is considered one of the most important parameter for optimization of chiral resolution (R s ) in MEKC. This is because pH usually alters both the charge of the analyte and/or chiral selector (surfactant) possessing ionizable groups as well as influencing the magnitude of electroosmotic flow (EOF).…”