Chiral CE–MS - Chiral Separations by Capillary Electrophoresis - page 376

100 100

Methadone
m

Tramadol
m

/ z : 310

/ z : 264

50 50

0.85%

0.75%

0.60%

0.75%

0
10 12 14 16 18 20 22 24 26 28

0
10 12 14 16 18 20 22 24 26 28

min

min

100

100

Fluoxetine
m / z : 310

Venlafaxine
m

/ z : 279

50

50

0.15%

0.85%

0.10%

0.75%

0
10 12 14 16 18 20 22 24 26 28

0
10 12 14 16 18 20 22 24 26 28

min

min

FIGURE 13.4 Chiral CE-ESI-MS analysis of tramadol, methadone, venlafaxine, and
l uoxetine with HS-γ-CD as the chiral selector. Lower traces: enantioseparations under
optimal conditions. Upper traces: ini nite enantioseparations. The ini nite enantioselectiv-
ity was achieved with different chiral selector concentrations for each enantiomer, but the
preferentially bonded enantiomer never reached the MS source. (From Rudaz, S. et al.,
Electrophoresis , 24, 2633, 2003. With permission.)

i rst choice in CE-UV when a rapid screening of various chiral compounds (acidic,
neutral, and basic) is needed [107,108]. Due to their high afi nity toward basic com-
pounds, excellent stereoselective resolutions were obtained in CE-MS with HS-

-CD
for several cationic pharmaceutical compounds including tramadol and its phase I
metabolites, MTD, venlafaxine, and l uoxetine [109]. An increase in the HS-

γ

-CD
concentration counter-balanced the negative inl uence of the nebulization gas pres-
sure, allowing a high signal-to-noise ratio as well as a stable electrospray current
[110,111]. When studying the impact of the selector concentration on the chiral reso-
lution, the authors were able to determine a CD concentration, which allowed for the
detection of only one enantiomer. In fact, a i ne-tuning of the HS-

γ

-CD concentra-
tion led to a situation where one enantiomer migrated toward the cathode while the
other one migrated toward the anode, as presented in Figure 13.4. This phenomenon
could be simply explained by differences in their respective charge, i.e., without the
need of any other counter-effect, such as counter-pressure or counter-electroosmotic
l ow. This ini nite enantiomeric resolution was anticipated by Williams and Vigh
[112] within the “charged resolving agent migration” (CHARM) model. It corre-
sponds to the chiral selector concentration where the apparent enantiomeric mobili-
ties are opposite for the two enantiomers. One enantiomer migrates in the MS side
while the other counter-migrates with the negatively charged CD. In the PFT, the
separation process occurs inside the plug of the BGE containing the chiral selector.

γ