β-环糊精毛细管电色谱法拆分和测定马尼地平、尼卡地平对映体

doi:10.3724/SP.J.1095.2014.40059

摘要/Abstract

摘要： 采用溶胶-凝胶法制备对硝基苯氨基甲酸酯化β-环糊精毛细管开管柱(NCDP)，建立了分别拆分钙离子阻滞剂盐酸马尼地平和盐酸尼卡地平对映体的毛细管电色谱方法。采用红外光谱、扫描电子显微镜对其进行了必要的结构及形态表征。在极性有机模式下，考察了有机溶剂的组成及含量、三乙胺和冰醋酸的含量、运行电压、温度对手性分离的影响。优化的条件为：温度20℃，检测波长236 nm，压力进样(3.448 kPa×3 s)，盐酸马尼地平在乙腈-甲醇-三乙胺-冰醋酸(体积比57∶43∶0.05∶0.07)流动相中，运行电压25 kV时，分离度(RS)为1.39；盐酸尼卡地平在乙腈-甲醇-三乙胺-冰醋酸(体积比55∶45∶0.05∶0.08)流动相中，运行电压20 kV时，分离度为1.30。上述两种地平对映体保留时间和峰面积的RSD分别小于1.2%和5.6%(n=5)，表明所制备的电色谱柱有良好的稳定性。盐酸马尼地平的拆分时间＜5 min，盐酸尼卡地平的拆分时间＜7 min，有利于建立快速测定其对映体含量的方法。盐酸马尼地平和盐酸尼卡地平在5.2~125 mg/L范围内线性关系良好(r≥0.9969)，检测限分别为1.8和2.3 mg/L(S/N=3)。初步将NCDP柱用于盐酸马尼地平片和盐酸尼卡地平缓释胶囊中对映体含量的测定。

关键词: 开管毛细管电色谱法, 溶胶-凝胶法, &, beta, -环糊精衍生物, 手性分离, 盐酸尼卡地平和盐酸马尼地平

Abstract: The separation and determination methods of calcium antagonists manidipine hydrochloride and nicardipine hydrochloride enantiomers were developed by open-tubular capillary electrochromatography(CEC), respectively. A new capillary column with p-nitrophenylcarbamation β-cyclodextrin was prepared by sol-gel method. The sol-gel modified with cyclodextrin derivative was characterized by infrared spectroscopy(IR) and scanning electron microscopy(SEM). In polar organic mode, the effect of the volume fraction and concentration of added triethylamine and glacial acetic acid, the content of organic solvents, the operating voltage, and temperature on the resolution(RS) were investigated. The optimized conditions were at 20 ℃, detection wavelength at 236 nm, and injection pressure at 3.448 kPa×3 s. The compositions of mobile phases were V(MeOH)∶V(ACN)∶V(TEA)∶V(HOAc)=57∶43∶0.05∶0.07 for manidipine hydrochloride and V(MeOH)∶V(ACN)∶V(TEA)∶V(HOAc)=55∶45∶0.05∶0.08 for nicardipine hydrochloride. The resolution(Rs) of manidipine hydrochloride was 1.39 at 25 kV. The resolution(Rs) of nicardipine hydrochloride was 1.30 at 20 kV. The RSDs of retention time and peak area were less than 1.2% and 5.6%(n=5) for the drugs, respectively. It was indicated that new column has stable electrochromatography performance. The single run time were less than 5 min for manidipine hydrochloride and less than 7 min for nicardipine hydrochloride. Good linearity were observed in the concentration range of 5.2~125.0 mg/L with correlation coefficients 0.9969 or more for both drug enantiomers. The limit of detection values were 1.8 mg/L for manidipine and 2.3 mg/L for nicardipine, respectively. The nitrophenyl carbamated β-cyclodextrin phase(NCDP) column were preliminarily used for determinations of manidipine hydrochloride and nicardipine hydrochloride tablet and capsule.

Key words: opened-tubular capillary electrochromatography, sol-gel, &, beta, -cyclodextrin derivative, chiral separation, manidipine hydrochloride and nicardipine hydrochloride

中图分类号:

O657

聂桂珍, 李来生, 程彪平, 周仁丹, 张宏福. β-环糊精毛细管电色谱法拆分和测定马尼地平、尼卡地平对映体[J]. 应用化学, DOI: 10.3724/SP.J.1095.2014.40059.

NIE Guizhen, LI Laisheng*, CHENG Biaoping, ZHOU Rendan, ZHANG Hongfu. Preparation of β-Cyclodextrin Capillary Column for Enantioseparation and Determination of Nicardipine and Manidipine by Capillary Electrochromatography[J]. Chinese Journal of Applied Chemistry, DOI: 10.3724/SP.J.1095.2014.40059.

参考文献

[1] Sennappan K T C,Yong E L,Gong Y H. Application of Bromoacetate-substituted β-CD-bonded Silica Particles as Chiral Stationary Phase for HPLC[J]. J Sep Sci,2010,33(1):74-78.

[2] LAN Weimin,XU Bingxin,AN Weiping. Content Determination of Main Components of Manidipine Hydrochlorid Tablets by HPLC[J]. China Pharm,2011,22(29):2767-2768(in Chinese).

兰为民,徐炳欣,安卫平. HPLC法测定盐酸马尼地平片中主药的含量[J]. 中国药房,2011,22(29):2767-2768.

[3] Inotsume N,Iwaoka T,Honda M,et al. Pharmacokinetics of Nicardipine Enantiomers in Healthy Young Volunteers[J]. Eur J Clin Pharm,1997,52(4):289-292.

[4] Nobuo I,Masahiro N. Stereoselective Determination and Pharmacokinetics of Dihydropyridines:An Updated Review[J]. J Biochem Biophys Methods,2002,54:255-274.

[5] Richy F F,Laurent S. Efficacy and Safety Profiles of Manidipine Compared with Amlodipine:A Meta-analysis of Head-to-head Trials[J]. Blood Pressure,2011,20(1):54-59.

[6] Shah S K,Asnani A J,Kawade D P,et al. Simultaneous Quantitative Analysis of Olmesartan Medoxomil and Amlodipine Besylate in Plasma by High-performance Liquid Chromatography Technique[J]. J Young Pharm,2012,4(2):88-94.

[7] Cui Y,Ma X,Zhao M,et al. Combined Use of Ionic Liquid and Hydroxypropyl-β-Cyclodextrin for the Enantioseparation of Ten Drugs by Capillary Electrophoresis[J]. Chirality,2013,25(7):409-414.

[8] Dai Z,Pittman C U,Li T. Enantiomeric Recognition of Racemic 4-Aryl-1,4-dihydropyridine Derivatives via Chiralpak AD-H Stationary Phases[J]. Chirality,2012,24(10):854-859.

[9] LI Chengping,ZENG Huaichao,LU Lin,et al. Study on the Chiral Resolution of Dihydropyridine Calcium Antagonists Manidipine and Clinidipine Enantiomers[J]. Chinese J Pharm Anal,2010,30(4):661-663(in Chinese).

李成平，曾怀超，鲁琳，等. 二氢吡啶钙拮抗剂马尼地平和西尼地平对映体的手性拆分研究[J]. 药物分析杂志,2010,30(4):661-663.

[10] Auditore R,Santagati N A,Aturki Z,et al. Enantiomeric Separation of Amlodipine and Its Two Chiral Impurities by Nano-liquid Chromatography and Capillary Electrochromatography Using a Chiral Stationary Phase Based on Cellulose Tris(4-chloro-3-methyl phenylcarbamate)[J]. Electrophoresis,2013,34(17):2593-2600.

[11] FU Qiang,HE Langchong. Enantiomeric Separation of Nicardipine by High Performance Liquid Chromatography Using Ovoglycoprotein as Stationary Phase[J]. Chinese J Anal Chem,2005,33(12):1779-1782(in Chinese).

傅强，贺浪冲. 卵类糖蛋白手性柱拆分钙离子拮抗剂尼卡地平对映体[J]. 分析化学，2005,33(12):1779-1782.

[12] Yamaguchi M,Yamashita K,Aoki I. Determination of Manidipine Enantiomers in Human Serum Using Chiral Chromatography and Column-switching Liquid Chromatography[J]. J Chromatogr B,1992,575(1):123-129.

[13] Uno T,Ohkubo T,Sugawara K. Enantioselective High-performance Liquid Chromatographic Determination of Nicardipine in Human Plasma[J]. J Chromatogr B,1997,698:181-186.

[14] FU Xiaoshuai,GUO Wenwen,JIANG Zhen,et al. Enantiomeric Separation of Five Basic Drugs by Orthogonal High Performance Capillary Electrophoresis[J]. J Shenyang Pharm Univ,2013,30(5):351-355(in Chinese).

付小帅，郭雯雯，姜珍，等. 基于正交设计的毛细管电泳法分离尼卡地平等5种手性药物对映体[J]. 沈阳药科大学学报,2013,30(5): 351-355.

[15] CAI Cheng,WANG Yuanchao,DENG Fei. Study on the Enantiomeric Separation of Nicardipne, Nimodipine and Nitrendipine by Capillary Electrophoresis[J]. J Hangzhou Normal Univ,2012,11(2):122-125(in Chinese).

蔡诚，王园朝，邓飞. 尼卡地平、尼莫地平和尼群地平毛细管电泳手性拆分研究[J]. 杭州师范大学学报,2012,11(2):122-125.

[16] Ou J,Zhang Z,Lin H,et al. Polyhedral Oligomeric Silsesquioxanes as Functional Monomer to Prepare Hybrid Monolithic Columns for Capillary Electrochromatography and Capillary Liquid Chromatography[J]. Anal Chim Acta,2013,761:209-216.

[17] Ou J,Lin H,Tang S,et al. Hybrid Monolithic Columns Coated With Cellulose Tris(3,5-dimethylphenyl-carbamate) for Enantioseparations in Capillary Electrochromatography and Capillary Liquid Chromatography[J]. J Chromatogr A,2012,1269:372-378.

[18] LI Yingjie. Research of Capillary Electrochromatography Chiral Monolithic Column of Modified β-Cyclodextrin[D]. Haerbin:Heilongjiang University,2010(in Chinese).

李英杰. 改性β-环糊精毛细管电色谱手性整体柱研究[D]. 哈尔滨：黑龙江大学，2010.

[19] Wang Y,Xiao Y,Tan T T Y,et al. Application of Click-chemistry-based Perphenylcarbamated β-CD Chiral Stationary Phase in CEC[J]. Electrophoresis,2009,30(4):705-711.

[20] Liu H,Li X,Huang L,et al. An Open Tubular Capillary Electrochromatography Column with Porous Inner Surface for Protein Separation[J]. Anal Biochem,2013,442(2):186-188.