Optical isomer separation of potential analgesic drug candidates by using capillary electrophoresis.
Using cyclodextrin capillary zone electrophoresis (CD-CZE), baseline separation of synthetic potential analgesic drug diastereoisomer candidates 6,11-dimethyl-1,2,3,4,5,6-hexahydro-3-[(2'-methoxycarbonyl-2'-phenylc yclopropyl)methyl]-2,6-methano-3-benzazocin-8-ol (MPCB) and 6,11-dimethyl-1,2,3,4,5,6-hexahydro-3-[[2'-methoxycarbonyl-2'(4-chloroph enyl)cyclopropyl]methyl]-2,6-methano-3-benzazocin-8-ol (CCB) was achieved. Among the cyclodextrins tested (hydroxypropyl-, carboxymethyl- and sulfobutyl-beta-cyclodextrin (HP-beta-CD, CM-beta-CD and SBE-beta-CD)) SBE-beta-CD was found to be the most effective complexing agent, allowing good optical isomer separation. Resolution was also influenced by the CD concentration, pH of the buffer and presence of organic modifier in the background electrolyte. The optimum experimental conditions for the separation of studied analgesic drugs were found using 25 mM borate buffer at pH 9 containing 40 mM of SBE-beta-CD and 20% v/v of methanol. Using the above-mentioned background electrolyte, it was also possible to separate, in the same run, the enantiomers of normetazocine (NMZ) as well as the optical isomers of (+/-)-cis-2-chloromethyl-1-phenyl cyclopropancarboxylic acid methyl ester (PCE) or (+/-)-cis-2-chloromethyl-1-(4-chlorophenyl)cyclopropancarboxylic acid methyl ester (CPCE) reagents used in the synthesis of the studied analgesic drugs).
Ferrara
G
G
Istituto di Cromatografia del CNR, Area della Ricerca Di Roma, Monterotondo Scalo, Roma, Italy.
Santagati
N A
NA
Aturki
Z
Z
Fanali
S
S
D000701:Analgesics, Opioid / Q000032:analysis*; D002021:Buffers; D003496:Cyclazocine / Q000031:analogs & derivatives* / Q000032:analysis; D003505:Cyclodextrins; D019075:Electrophoresis, Capillary / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D000432:Methanol; D015394:Molecular Structure; D013237:Stereoisomerism; D047392:beta-Cyclodextrins
C110285:6,11-dimethyl-1,2,3,4,5,6-hexahydro-3-((2'-(methoxycarbonyl)-2'-phenylcyclopropyl)methyl)-2,6-methano-3-benzazocin-8-ol; D000701:Analgesics, Opioid; D002021:Buffers; D003505:Cyclodextrins; D047392:beta-Cyclodextrins; C093196:SBE4-beta-cyclodextrin; D003496:Cyclazocine; D000432:Methanol