Ferrara G, Santagati N A, Aturki Z, Fanali S
Istituto di Cromatografia del CNR, Area della Ricerca Di Roma, Monterotondo Scalo, Roma, Italy.
Electrophoresis. 1999 Sep;20(12):2432-7. doi: 10.1002/(SICI)1522-2683(19990801)20:12<2432::AID-ELPS2432>3.0.CO;2-B.
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).
采用环糊精毛细管区带电泳（CD-CZE）实现了合成潜在镇痛药物非对映异构体候选物6,11-二甲基-1,2,3,4,5,6-六氢-3-[(2'-甲氧基羰基-2'-苯基环丙基)甲基]-2,6-亚甲基-3-苯并氮杂环辛-8-醇（MPCB）和6,11-二甲基-1,2,3,4,5,6-六氢-3-[[2'-甲氧基羰基-2'(4-氯苯基)环丙基]甲基]-2,6-亚甲基-3-苯并氮杂环辛-8-醇（CCB）的基线分离。在所测试的环糊精（羟丙基-β-环糊精、羧甲基-β-环糊精和磺丁基-β-环糊精（HP-β-CD、CM-β-CD和SBE-β-CD））中，发现SBE-β-CD是最有效的络合剂，能实现良好的光学异构体分离。分离度还受环糊精浓度、缓冲液pH值以及背景电解质中有机改性剂的影响。使用pH 9的25 mM硼酸盐缓冲液，其中含有40 mM的SBE-β-CD和20%（v/v）的甲醇，找到了分离所研究镇痛药物的最佳实验条件。使用上述背景电解质，在同一次运行中还可以分离去甲美沙酮（NMZ）的对映体以及用于合成所研究镇痛药物的(+/-)-顺-2-氯甲基-1-苯基环丙烷羧酸甲酯（PCE）或(+/-)-顺-2-氯甲基-1-(4-氯苯基)环丙烷羧酸甲酯（CPCE）试剂的光学异构体。
