Chiral Separation and Detection of Terbutaline and Ephedrine by Capillary Electrophoresis Coupled with Ion Spray Mass Spectrometry

Abstract

The enantiomers of both terbutaline and ephedrine were separated by capillary electrophoresis using electrolyte solutions of heptakis(2,6-di-O-methyl)-beta-cyclodextrin in low pH buffers. The analytes were detected by ion spray mass spectrometry using selected ion monitoring or by selected reaction monitoring in the positive ion mode. Both the free drug enantiomers and the noncovalent enantiomer-cyclodextrin inclusion complexes for terbutaline can be detected simultaneously using this method. The feasibility of using CE/MS for chiral purity determination is demonstrated. In addition, a comparison of UV detection versus mass spectrometry detection for a spiked urine sample is included to demonstrate the selectivity and sensitivity advantages of the mass spectrometer as a CE detector.

Sensitive chiral analysis by capillary electrophoresis

“…Then, the ionization of the analytes, normally by ESI, is performed before the MS detection (usually by quadrupole or IT). Although in some works a low concentration of chiral selector is directly introduced in the MS obtaining satisfactory results [135], in most works the introduction of the chiral selector in the MS detector is avoided or chiral selectors compatible with MS detection, such us crown ethers [136,137] are employed. In fact, the introduction of nonvolatile chiral selectors in MS can affect the sensitivity and stability of this detector [138].…”

“…Thus, two different derivatization protocols for amino acids using dansyl chloride (DNS) and FITC were compared observing better mass sensitivity for FITC-amino acids (LODs in the mM range) [139]. CE-ESI-MS has also been used for the sensitive determination of chiral compounds in biological samples such as urine [135,140,141], plasma [142], serum [143], and in vivo samples [144], and for the identification of drugs and their metabolites [145,140].…”

Chiral analysis of pollutants and their metabolites by capillary electromigration methods

“…Chiral analysis by CE-MS has also been proposed using CDs as chiral selectors [58,59]; however, the use of CDs as well as other nonvolatile additives can contaminate the ion source, reducing considerably the MS signal intensity and, as a result, decreasing the sensitivity. Some strategies have been proposed to avoid these problems, the partial filling technique being the most frequently applied.…”

18 Coupling CE and microchip-based devices with mass spectrometry

“…First experiments in chiral CZE2MS with CD were achieved by Sheppard et al 179 in 1995, who demonstrated selectivity and sensitivity advantages of MS for the separation of terbutaline and ephedrine enantiomers. An important gain in sensitivity (1000-fold) was obtained by MS compared to UV detection.…”