Enantiomeric Separation of Galantamine in Drug for Alzheimer's Disease and Its Quality Control by Capillary Electrophoresis

Abstract

Abstract: A method for capillary electrophoretic enantiomeric separation of a novel drug for Alzheimers disease, Galantamine, has been established with α-cyclodextrin as the chiral additive. General equations and data analysis approach are presented to relate molibilities to equalibrium constants in simple binding equilibria and used to determine bonding constants and thermodynamic parameters for host-guest complexation of galantamine enantiomers with cyclodextrin selector. The effects of cyclodextrin concentration and type, buffer concentration and its pH, and separation voltage were investigated. The mechanism of enantioselectivity is discussed by combining with the computer simulating conformational analysis. The maximal resolution of 3.60 was obtained . The bonding constants of host-guest complex of galantamine enantiomers with α-cyclodextrin, K_R-CD and K_S-CD, is 33.98 L/mol and 23.90 L/mol, respectively. The established method was successfully applied to the detect ion of the non-effective component in the raw material of galantamine. Ten structural analogues were found, and the content of R enantiomer is 0.82%. The concentration linear rang is 0.015—1.0 mmol/L with the analysis precision of 0.20% and 2.6% for the measurement of migration time and peak area, respectively. Thus, the method could be used as a rapid and reliable tool for quantity control of the drug.

Key words: Galantamine, Cyclodextrin, Bonding constant, Chiral separation, Pharmaceutical analysis

CLC Number:

O657.8

TrendMD:

YAN Liu-Shui, ZHAO Ji-Yuan, LUO Guo-An, SUN Ming, WANG Yi-Ming, YANG Xue-Dong . Enantiomeric Separation of Galantamine in Drug for Alzheimer's Disease and Its Quality Control by Capillary Electrophoresis[J]. Chem. J. Chinese Universities, 2004, 25(2): 256.

References

[1] Pearson V.E..Ann.Pharm aco ther.[J],2001,35(11);1 406—1 413 [2] MA Guang-En(马广恩).Progress in Pharm aceutical Science(药学进展)[J],1998,2(3);153—156 [3] GUO Li(郭　例).Fo reign Medical Science Section on Pharmacy(国外医学2药学分册)[J],2001,28(2);128—129 [4] Chinese National Pharm acopoeia Comm ittee(国家药典编委会).The Pharm acopoeia of Peop le's Republic of China,PartⅡ(中华人民共和国药典,二部)[M],Beijing;Chem ical Industry Press,2000;490—491 [5] Claessen s H.A.,Lemm en s A.A.G.,Sparidan s R.W.et al..Chromatograph ia[J],1988,26;351—358 [6] WeiW.,Luo G.A..J.High Reso l.Ch rom atogr.[J],1998,21(8);440—444 [7] Ward T.M..Anal.Chem.[J],2002,74(12);2 863—2 872 [8] Chankvetadze B.,Blaschke G..J.Ch rom atogr.A[J],2001,906;309—363 [9] CHEN Yi(陈　义),LU Xiao-Ning(卢小宁).Chem.J.Ch inese Universities(高等学校化学学报)[J],2002,23(5);822—824 [10] Vincen t J.B.,Vigh G..J.Ch rom atogr.A[J],1998,817;105—111 [11] Blanco M.,Coello J.,Iturriga H.et al..J.Ch rom atogr.A[J],1998,799;301—307 [12] Foulon C.,Goo ssen s J.F.,Fourm ain traux E.et al..Electropho resis[J],2002,23;1 121—1 128 [13] Raw jee Y.Y.,Staerk D.U.,Vigh Gy..J.Ch rom atogr.[J],1993,635;291—306 [14] Kuhn R.,Ern i F..Anal.Chem.[J],1992,64;2 815—2 820 [15] Penn S.G.,Bergstrom E.J.,Goodall D.M.et al..Ana.lChem.[J],1994,66;2 866—2 873 [16] Arm strong D.W.,Ward T.J.,Arm strong R.D.et al..Science[J],1986,232(30);1 132—1 135 [17] XIA Bao-Yun(夏保云),CAI Wen-Sheng(蔡文生),PAN Zhong-Xiao(潘忠孝)et al..Chem.J.Ch inese Universities(高等学校化学学报)[J],2002,23(6);1 122—1 125 [18] ZHANG Jun-Mei(张俊梅),W ANG Ming-Xin(王明新),SHEN Ya-Wei(申雅维)et al..Ch inese J.Pharm aceutical Ana.l(药物分析杂志)[J],1999,19(6);399—402 [19] FANG Ling(方　玲).Ch inese J.Clin ical Pharm acy(中国临床药学杂志)[J],2001,10(6);381—383