Chiral CE–MS - Chiral Separations by Capillary Electrophoresis - page 375

and therefore low electrophoretic currents are generated [97]. Successful applications
for anionic and particularly cationic analytes were published with the partial i lling
countercurrent technique (PFT-CC), using both positively and negatively charged chi-
ral selectors. Because more than 85% of the ionizable analytes possess a basic func-
tion, the PFT-CC with a negatively charged chiral selector was by far the most studied
approach. Carboxymethyl- β -CD (CM- β -CD), a negatively charged chiral selector at

pH > 3, and sulfobutylether- -CD) were the most used negatively charged

selectors during the early times of chiral CE-MS. Later, highly sulfated cyclodextrins
(HS-CD) introduced by Vigh and coworkers [98-100] as single isomers, and from
commercial sources as mixtures of randomly sulfated CD [67,68,101,102], emerged as
the i rst choice for the separation of cationic compounds.
CM-

β -CD (SBE- β

-CD were used for the i rst time in 1998 for the separation of
etilefrine, mianserine, dimethindene, and chloropheniramine by Blaschke and cowork-
ers [103]. The chiral resolution of venlafaxine, a second generation antidepressant drug
and its major active metabolite, O -desmethyl venlafaxine was successfully achieved
with CM-

β -CD and SBE- β

-CD was also employed for the analysis
of methadone (MTD), for which the use of a PVA-coated capillary was mandatory
to avoid the presence of the CD in the MS source. The sensitivity was increased by
a factor of 10 compared to UV detection, allowing for the therapeutic drug monitor-
ing of MTD. Some time later, MTD was selected by Rudaz et al. [104] as a model
compound for a chemometric study of the parameters involved in enantioseparation
by CE-ESI-MS using three different CD, including CM-

β -CD by Cherkaoui et al. [89]. CM- β

-CD. The
evaluation of three important experimental parameters regarding PFT, namely, nebu-
lization gas pressure, CD concentration, and separation zone length, was carried out.
A sequential experimental design strategy was achieved i rst using a full factorial
design. In a second step, additional experiments were completed to fully model the
chiral resolution and to obtain response surfaces thanks to a second degree design.
The results obtained coni rmed that the nebulization pressure dramatically affected
the quality of the enantiomeric separation, while the separation zone length was of
minor importance. The hydrodynamic l ow induced by the sheath-liquid interface
was less detrimental when a negatively charged CD was used, demonstrating another
benei t of the CC migration process towards the regular PFT. It should be noted that
CM-

β -CD and SBE- β

-CD can be only partially negatively charged and used as a neutral or charged
selector, while the SBE-

β

-CD
was chosen for the stereoselective PFT-CC analysis of tramadol and its phase I metab-
olites in biological matrices [105]. The SIM acquisition allowed the unambiguous
determination of each analyte in spite of the peak overlapping, and it demonstrated the
high selectivity of MS compared to conventional detectors. Among other investigated
CDs, Cherkaoui and Veuthey [106] demonstrated that SBE-

β -CD is ionized regardless of the pH in the BGE. SBE- β

-CD was well suited
for the simultaneous enantioseparation of bupivacaine, mepivacaine, prilocaine, and
ketamine. The enantiomeric determination of atropine in plant extracts without any
additional preconcentration step was achieved with SBE-

β

-CD [89]. By using MS, a
10 3 factor sensitivity was achieved compared to UV, with a detection concentration at
the ppb level. After correction with homatropine as IS, the migration time and peak
area repeatabilities were found to be 0.2% and 5.5%, respectively.
As previously mentioned, the powerful resolving power of HS-CD has largely
contributed to their use in PFT-CC. These selectors were rapidly considered as a

β