Enantioseparations of Dihydropyridine Drugs by Sulfobutyl Ether-β-Cyclodextrin Modified Capillary Electrochromatography†

doi:10.7503/cjcu20140099

Abstract

Abstract:

A novel sulfobutyl ether-β-cyclodextrin(SBE-β-CD) capillary electrochromatographic column(SECDP) was prepared by glycidyl methacrylate polymer matrix in situ and its modification. Its basic structure was characterized by infrared spectroscopy(IR) and scanning electron microscopy(SEM). The sulfonic acid group could provide a enough and stable positive electroosmotic flow(EOF). Enantioseparations of 10 kinds of chiral dihydropyridine drugs including amlodipine, nimodipine, nicardipine and so on were achieved by synergistic effects of SBE-β-CD in the stationary and mobile phases. Some effect factors such as the chiral additive concentration, pH value, the applied voltage, temperature and organic modifier content were optimized. The optimal separation conditions were as follows: the mobile phase consisting of 20 mmol/L NaH₂PO₄(pH=4.0), containing 4.0 mmol/L of SBE-β-CD, acetonitrile volume content of 10% to 25%, an applied voltage of 15—25 kV, the temperature at 15 ℃, electrokinetic injection 2 kV×5 s and the detection wavelength at 236 nm. Under the above conditions, the separation resolutions(R_s) of dihydropyridine enantiomers were up to 3.62, the column efficiency were about 61011/m, and the analysis time were generally between 6—15 min. Based on the data of chromatographic separations, the related chiral separation mechanism was also discussed. The preparation method of SECDP and chiral separation method were rapid, simple, reprodu-cible and suitable for fast enantioseparations and montoring of chiral dihydropyridine drugs.

Key words: Capillary electrochromatography, Glycidyl methacrylate polymer matrix in situ, Sulfobutyl ether-β, -cyclodextrin, Chiral separation, Dihydropyridine drug

CLC Number:

O657

TrendMD:

NIE Guizhen, LI Laisheng, CHENG Biaoping, ZHOU Rendan, ZHANG Hongfu. Enantioseparations of Dihydropyridine Drugs by Sulfobutyl Ether-β-Cyclodextrin Modified Capillary Electrochromatography^†[J]. Chem. J. Chinese Universities, 2014, 35(7): 1414.

Figures/Tables 10

Fig.1 Chemical structures of dihydropyridine drugs

Fig.2 Preparation route of open-tublar capillary column modified with sulfbutyl ether-β-cyclodextrin

Fig.3 FTIR spectra of SECDP(a) and GMA-EDMA(b) before modification

Fig.4 SEM images of inner wall in capillary column before(A) and after(B) modification

Fig.5 Effects of pH value(A) and organic solvent content(B) on the EOF

Table 1 Effects of pH values on the separationparameters

pH	t₁	t₂	α	R_S
2.5	9.03	10.14	1.46	1.85
3.5	7.34	7.88	1.45	1.84
4.0	6.38	7.55	1.46	1.84
4.5	4.22	4.63	1.18	1.24
6.5	3.90	3.90	1.00	0

Fig.6 Effect of acetonitrile content on the enantioseparation of amlodipine besylate a. 18%; b. 22%; c. 25%. d. 30%. Conditions: 20 mmol/L NaH2PO4(pH=4.0), 4.0 mmol/L SBE-β-CD, applied voltage 20 kV and temperature 15 ℃, injection: 2 kV×5 s.

Table 2 Reproducibilities of amlodipine enantiomers about retention time and peak area(n=5)

	RSD(%)
	t₁	t₂	A₁	A₂
Intra-day	1.09	1.24	4.35	4.48
Inter-day	1.21	1.56	5.54	5.65

Table 3 Enantioseparation results of dihydropyridine drugs*

Compound	t₁/min	t₂/min	R_s	N₁/(Plates·m^-1)	N₂/(Plates·m^-1)	ACN(%)	V/kV
Amlodipine besylate	6.38	7.55	1.84	22976	20054	22	20
Amlodipine mesylate	4.64	4.93	1.75	30261	29851	22	25
Nimodipine	7.04	7.87	3.62	61011	60034	20	25
Nicardipine	5.33	6.03	3.52	50142	49867	15	25
Manidipine	10.97	11.75	1.52	37072	35721	25	15
Benidipine	6.23	6.64	1.54	54853	52014	10	20
Cilnidipine	7.37	8.16	1.50	13795	12876	25	25
Nitredipine	11.88	12.56	1.15	25603	20230	10	15
Felodipine	15.90	16.76	1.14	12065	10274	18	25
Lercanidipine	5.70	6.13	0.63	11254	10235	12	25
Lacidipine	29.12	29.83	0.32	10242	10112	12	20

Fig.7 Electrochromatograms of some dihydropyridine enantiomers on SECDP (A) Amlodipine besytle; (B) amlodipine mesylate; (C) nimodipine; (D) nicardipine; (E) manidipine; (F) benidipine; (G) cilnidipine.

References 29

[1]	Ribeiro A. R., Afonso C. M., Castro P. M. L., Tiritan M. E., Ecotoxicol. Environ. Saf., 2013, 87, 108—114
[2]	Barnes B. J., Howard P. A., Lai S. M., Grauer D. W., Muehlebach G. F., Hosp. Pharm., 2012, 47(8), 617—625
[3]	Xiao M., Xu B. Y., Chen Y. B., Li S. Y., Contemp. Med., 2013, 19(15), 132—133
	(肖敏, 徐八一, 陈益彪, 李淑云. 当代医学, 2013, 19(15), 132—133)
[4]	Lu J., China Pharm., 2013, 22(4),86—87(卢军. 中国药业, 2013, 22(4), 86—87)
[5]	Yoon Y. J., Kim K. B., Kim H., Seo K. A., Kim H. S., Cha I. J., Kim E. Y., Liu K. H. Shin J. G., Drug Metab. Dispos., 2007, 35(9), 1518—1524
[6]	Inotsume N., Nakano M., J Biochem. Biophys. Methods, 2002, 54, 255—274
[7]	Uno T., Ohkubo T., Sugawara K., J. Chromatogr. B, 1997, 698(1/2), 181—186
[8]	Fu Q., He L. C., Chin. J. Anal. Chem., 2005, 33(12), 1779—1782
	(傅强, 贺浪冲. 分析化学, 2005, 33(12), 1779—1782)
[9]	Xu L. F., Lu Y., Li Y., Xu X., Chin. J. Chromatogr., 2010, 28(4), 426—429
	(徐丽芳, 鲁耀, 李奕, 许旭. 色谱, 2010, 28(4), 426—429)
[10]	Tang X. D., Wang S. Y., Cong J. X., Wang Z. C., Chin. J. Spectr. Lab., 2011, 28(5), 2573—2577
	(唐晓丹, 王绍艳, 丛景香, 王智超. 光谱实验室, 2011, 28(5), 2573—2577)
[11]	Li C. P., Zeng H. C., Lu L., Gao W. L., Shan W. G., Chin. J. Pharm. Anal., 2010, 30(4), 661—663
	(李成平, 曾怀超, 鲁琳, 高伟梁, 单伟光. 药物分析杂志, 2010, 30(4), 661—663)
[12]	Lammerhofer M., Gyllenhaal O., Lindner W., J. Pharm. Biomed. Anal., 2004, 35(2), 259—266
[13]	Chen J., Yao X. N., Lin L. N., Guo X. J., J. Shenyang Pharm. Univ., 2010, 27(2), 132—134
	(陈静, 姚鑫宁, 林丽娜, 郭兴杰. 沈阳药科大学学报, 2010, 27(2), 132—134)
[14]	Cucinotta V., Contino A., Giuffrida A., Maccarrone G., Messina M., J. Chromatogr. A, 2010, 1217(7), 953—967
[15]	Juvancz Z., Kendrovics R. B., Lvanyi R., Szente L., Electrophoresis, 2008, 29(8), 1701—1712
[16]	Wang R., Jia Z. P., Fan J. J., Chen L. R., Xie H., Ma J., Ge X., Zhang Q., Ao Y., Wang J., Chromatographia, 2007, 65(9/10), 575—579
[17]	Li B. H., Yang G. L., Wang D. X., Zhang Z. F., Chen Y., Chin. J. Chromatogr., 2002, 20(4), 338—340
	(李保会, 杨更亮, 王德先, 张哲峰, 陈义. 色谱, 2002, 20(4), 338—340)
[18]	Hu Y. L., Zhao M., Guo W. W., Zhang L. J., Xu S. Y., Guo X. J., J. Shenyang Pharm. Univ., 2013, 30(2), 114—119
	(胡艳丽, 赵旻, 郭雯雯, 张丽娟, 徐淑英, 郭兴杰. 沈阳药科大学学报, 2013, 30(2), 114—119)
[19]	Fakhari A. R., Nojavan S., Haghgoo S., Mohammadi A., Electrophoresis, 2008, 29(22), 4583—4592
[20]	Xu S. J., Wu M. J., Chin. J. Anal. Chem., 2004, 32(1), 46—49
	(许菽娟, 吴明嘉. 分析化学, 2004, 32(1), 46—49)
[21]	Cai C., Wang Y. C., Deng F., J. Hangzhou Normal Univ., 2012, 11(2), 122—125
	(蔡诚, 王园朝, 邓飞. 杭州师范大学学报, 2012, 11(2), 122—125)
[22]	Li Y., Zhu P. Y., Song F. Y., Chin. J. Pharm.Anal., 2011, 31(2), 306—310
	(李艺, 朱培仪, 宋粉云. 药物分析杂志, 2011, 31(2), 306—310)
[23]	Van E. A., Detaevernier M. R., Michotte Y., J. Pharm. Biomed. Anal., 2004, 36(4), 799—805
[24]	Zhang W.B., The Theoretical Basis for Capillary Electrochromatography, Science Press, Beijing, 2006, 23—35
	(张维冰. 毛细管电色谱理论基础, 北京: 科学出版社, 2006, 23—35)
[25]	Wren A. C., Rowe C. R., J. Chromatogr. A, 1992, 603(1/2), 235—241
[26]	Wang S. Y., Dai Y., Wu J. H., Zhou J., Tang J., Tang W. H., J. Chromatogr. A, 2013, 1227, 84—92
[27]	Li Y. J., Song C. H., Zhang L. Y., Zhang W. B., Fu H. G., Talanta, 2010, 80(3), 1378—1384
[28]	Xia D. H., Ren X. D., Jiao L., Li H., Chem. Res. Chinese Universities, 2012, 28(2), 282—286
[29]	Yuan R., Wang Y., Ding G., Anal. Sci., 2010, 26(9), 943—947
	(Ed.: N, K)