Enantioseparation of anaesthetic drugs by capillary zone electrophoresis using cyclodextrin-containing background electrolytes.
The enantiomers of five racemic anaesthetic drugs were resolved with cyclodextrins using capillary zone electrophoresis. Parameters which affected the chiral resolution, such as type and concentration of cyclodextrin, temperature, and addition of organic modifier were investigated. The results show that the enantiomeric discrimination of the solutes is influenced by the structural shape of the solute molecules, separation temperature, and type of cyclodextrin. It was found that alpha-cyclodextrin was the best enantioselector for resolution of prilocaine and ketamine, while the enantiomers of mepivacaine, ropivacaine, and bupivacaine were resolved with beta-cyclodextrin and/or modified beta-cyclodextrins, i.e., methyl- and 2-hydroxypropyl-beta-cyclodextrin, as chiral selectors. The length of the alkyl chain on the amino group of the drug molecule had a strong effect on the enantioresolution of mepivacaine, ropivacaine, and bupivacaine. Baseline separation of racemic ketamine was achieved with alpha- and methyl-beta-cyclodextrin at 15 degrees C. Addition of 5 M urea to the running buffer containing beta-cyclodextrin at high concentrations resulted in the enantioseparation of prilocaine, mepivacaine, and ketamine. Enantioresolution was improved upon the addition of 10% methanol to the buffer containing urea and beta-cyclodextrin. Generally, the complex formed between the S-enantiomers and modified beta-cyclodextrins was stronger than the corresponding R-forms. An exception was prilocaine where the R-form gave a more stable complex both with alpha- and beta-cyclodextrin.
Amini
A
A
Medical Products Agency, Division of Chemistry and Pharmacy, Uppsala, Sweden. ahmad.amini@farmkemi.uu.se
Sörman
U P
UP
Lindgren
B H
BH
Westerlund
D
D
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000577:Amides / Q000737:chemistry / Q000302:isolation & purification; D000777:Anesthetics / Q000737:chemistry / Q000302:isolation & purification*; D000778:Anesthetics, Dissociative / Q000737:chemistry / Q000302:isolation & purification; D002045:Bupivacaine / Q000737:chemistry / Q000302:isolation & purification; D003505:Cyclodextrins; D004573:Electrolytes; D019075:Electrophoresis, Capillary / Q000379:methods*; D007649:Ketamine / Q000737:chemistry / Q000302:isolation & purification; D008619:Mepivacaine / Q000737:chemistry / Q000302:isolation & purification; D015394:Molecular Structure; D011318:Prilocaine / Q000737:chemistry / Q000302:isolation & purification; D000077212:Ropivacaine; D047391:alpha-Cyclodextrins; D047392:beta-Cyclodextrins
D000577:Amides; D000777:Anesthetics; D000778:Anesthetics, Dissociative; D003505:Cyclodextrins; D004573:Electrolytes; D047391:alpha-Cyclodextrins; D047392:beta-Cyclodextrins; C479658:hydroxypropyl-alpha-cyclodextrin; C108732:methyl-beta-cyclodextrin; D011318:Prilocaine; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D007649:Ketamine; D000077212:Ropivacaine; D008619:Mepivacaine; C031215:betadex; D002045:Bupivacaine; C032613:alpha-cyclodextrin