Separation of drugs by capillary electrophoresis, Part 10. Permethyl-alpha-cyclodextrin as chiral solvating agent

Abstract

Following the German-Chinese Drug Screening Program, 86 racemic drugs were investigated in capillary zone electrophoresis in the presence of the chiral solvating agent (CSA) hexakis-(2,3,6-tri-O-methyl)-alpha-cyclodextrin (TM-alpha-CD). Of the 86 drugs, 23 were separated into enantiomeric pairs. A comparison of the migration separation factors (alpha(m)) and the migration retardation factors (Rm) with previously published data for native alpha-CD revealed that the 'upper-rim' hydroxyl groups do not necessarily facilitate the recognition of the drug enantiomers by the chiral host. In contrast, an overall increase in affinity for the permethylated host led to a higher rate of successful enantiomer separations. A key substructure (4H) was identified in the analyte structure domain, with a crucial influence on the behavior of a particular drug.

Separation of Enantiomers of Drugs by Capillary Electrophoresis with Permethyl-gamma-Cyclodextrin as Chiral Solvating Agent

“…In contrast to the findings with a-CD and TM-a-CD [17], chiral recognition by TM-c-CD is not higher than by native c-CD, but even somewhat lower. At first glance, this can be seen from the a m values, see Tables 1 and 2.…”

“…In contrast to the findings with the a-analogs [17], the R m values are generally much higher for native c-CD than for TM-c-CD. The chiral separation status with c-CD and TM-c-CD is depicted in Figure 4.…”

“…For TM-c-CD (Figure 7), the R m range is relatively narrow for both classes of analytes (black and red dots), and the most succussful separations occur for racemates where 4H is present. This behavior is in contrast to the findings with the a-analoga [17], where affinity and enantioselectivity are more narrow for native a-CD. Frequency functions of the analytes in various ranges of R m are shown in Figures 8 and 9.…”

“…For analytes with the 4H substructure (black dots), the maximum R m values are approximately 2.7 with TM-c-CD and 4.2 with c-CD, respectively. Similar to the pattern found for the a-analoga[17], the drugs that do not contain 4H (red dots) are concentrated in the smaller R m region, while the black dots (4H present) are distributed more evenly over a wide range of R m values.…”

“…As compared to native c-CD, the permethylated derivative TM-c-CD does not lead to a higher chance of separation (R suc ), however, on the avarage it did lead to higher migration separation factors (a m ) for analytes where 4H is present A plot of the migration retardation factor R m with TM-c-CD versus R m with c-CD is shown in Figure 5. In contrast to the a-analogs [17], the majority of dots is located below the diagonal line, i. e., in the lower right part of the diagram. Apparently, the interaction of the analytes with c-CD on the average is stronger than with TM-c-CD, which is in good agreement with the pattern displayed in Likewise, plots of the migration separation factors (a m ) versus the retardation factor (R m ) reveal distinct differences for the two CSAs.…”