毛细管电泳法分离5种β受体阻滞剂
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摘要
采用5种β受体阻滞剂为手性分离对象,以羧甲基-β-环糊精(CM-β-CD)为手性选择剂进行毛细管电泳分离研究,系统考察了CM-β-CD浓度、pH值、分离电压、缓冲液种类对拆分效果的影响,探讨作用机制。结果表明,在0.05%～0.8%范围内,普萘洛尔对映体的分离度和分析时间随CM-β-CD浓度增加呈线性增长(相关系数r均为0.988)。增加pH值和增大电压,均能加快分析速度,提高柱效,但选择因子和分离度下降(以5mmol/L磷酸盐作为缓冲液(pH5.5),以0.2%～0.4%CM-β-CD作为手性选择剂,分离电压为25kV,普萘洛尔、美托洛尔、阿替洛尔、倍他洛尔和卡拉洛尔5种药物的对映体分离度均大于1.5,分析时间在17分钟以内)。本研究建立的拆分方法简便、快速、分离度良好,适用于手性分离β受体阻滞剂。
Using 5 mmol/L phosphate as buffer solution(pH5.5),carboxymethyl-β-cyclodextrin(CM-β-CD)concentration from 0.2%to 0.4%,and the separation voltage of 25 kV,the enantiomers of propranolol,metoprolol,atenolol,betaxolol and carazolol are separated completely.The resolution is greater than 1.5,and the analysis time is within 17 minutes.The resolution and analysis time of propranolol enantiomers increase linearly with the increase of CM-β-CD concentration in the range of 0.05% to0.8%(the correlation coefficient is 0.988).Increasing pH value or voltage can reduce the analysis time and improve the column efficiency.However,the selection factor and the resolution decrease.This method is simple,rapid and of good resolution.It is suitable for chiral separation of beta blockers.
Using 5 mmol/L phosphate as buffer solution(pH5.5),carboxymethyl-β-cyclodextrin(CM-β-CD)concentration from 0.2%to 0.4%,and the separation voltage of 25 kV,the enantiomers of propranolol,metoprolol,atenolol,betaxolol and carazolol are separated completely.The resolution is greater than 1.5,and the analysis time is within 17 minutes.The resolution and analysis time of propranolol enantiomers increase linearly with the increase of CM-β-CD concentration in the range of 0.05% to0.8%(the correlation coefficient is 0.988).Increasing pH value or voltage can reduce the analysis time and improve the column efficiency.However,the selection factor and the resolution decrease.This method is simple,rapid and of good resolution.It is suitable for chiral separation of beta blockers.
引文
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[15]王建军,郑国钧,王佳亮,杨柳,吴襟,沙倩,孙万儒.β-受体阻滞剂及其类似物的毛细管电泳手性分离.分析化学,2001,(06):671-675.
[16]王兆昆,赵龙山,崔智,严加高,郭兴杰.磺酸化-β-环糊精为手性选择剂分离5种β-受体阻断剂类药物.沈阳药科大学学报,2015,32(12):962-966.
[17]冯颖.水相/非水相毛细管电泳中环糊精手性拆分β-受体阻滞剂机理研究.暨南大学,2015.
[18]李学仁,程庆春,杨跃伟,张云斌,尚素芬,王洪.高效毛细管电泳法研究美托洛尔、艾司洛尔和维拉帕米的对映体的手性分离.中国药学杂志,1999,(04):45-46.
[19]肖溶,杜培刚,罗月影,等.羧甲基-β-环糊精取代度对毛细管电泳手性拆分普罗帕酮和普萘洛尔对映体的影响.贵阳医学院学报,2010,35(2):144-150.
[20]吴晓苹,陈小燕,郑敏敏.毛细管电泳-安培检测法分离分析手性药物索他洛尔.分析化学,2010,38(12):1776-1780.
[21]彭佳伟,徐蕾,李小晨,等.基于离子液体辅助的毛细管电泳法手性拆分阿替洛尔对映异构体.化工时刊,2016,30(8):1-4.
[22]利健文.毛细管电泳手性拆分美托洛尔、阿普洛尔和卡替洛尔对映体.理化检验-化学分册,2010,46(2):175-177.
[23]韦寿莲,刘玲,严子军,等.鼠血中烯丙洛尔对映体的毛细管电泳分离与测定.分析测试学报,2010,29(5):488-492.
[24]王钰,杨思文,代语林,邓宁,王燕,何建波,朱燕舞.离子液体对毛细管电泳分离美托洛尔和普萘洛尔对映体的影响研究[J].药物分析杂志,2014,34(11):2091-2097.
[25]Wren S A C,Rowe R C.Theoretical aspects of chiral separation in capillary electrophoresis I,Initial evaluation of a model[J].Journal of Chromatography A,1992,(603):235-241.
[26]王益莹.正电型β-环糊精在毛细管电泳中对手性药物拆分的基础研究.南京理工大学,2015,硕士学位论文.
[2]Dinicolantonio J J,Fares H,Niazi A K,et al.β-Blockers in hypertension,diabetes,heart failure and acute myocardial infarction:a review of the literature[J].Open Heart,2015,2(1):000230.
[3]Pavlinov S A,Belolipetskaya V G,Piotrovskii V K,et al.Enantiomers of propranolol in the blood of patients with cardiovascular diseases during long-term therapy[J].Pharmaceutical Chemistry Journal,1990,24(1):17-19.
[4]Iha M H,Martinez A S,Bonato P S.Enantioselective analysis of atenolol in biologic fluids:comparison of liquid-liquid and solid-phase extraction methods[J].Journal of ChromatographyB,2002,767(1):1-9.
[5]Kendall M J.Clinical relevance of pharmacokinetic differences betweenbeta blocker[J].American Journal of Cardiology,1997,80(9):15.
[6]Mehvar R,Brocks D R.Stereospecific pharmacokinetics and pharmacodynamicsof betaadrenergic blockers in humans[J].Journal of pharmacy&pharmaceutical sciences,2001,4(2):185.
[7]Walle T.Stereochemistry of the in vivo disposition and metabolism of propranolol in dog and man using deuterium-labeled pseudoracemates[J].Drug metabolism and disposition:the biological fate of chemicals,1985,13(3):279-282.
[8]Kitaori K,Furukawa K,Yoshimoto H,et al.Regioselective Nucleophilic Reactions of Phenolswith OxiranesLeading to Enantiopureβ-blockers[J].Tetrahedron,1999,55(50):14381-14390.
[9]Brown R A,IIg K J,Chen A F,et al.Dietary Mg2+supplementationrestores impaired vasoactive responses in isolatedrat aorta induced by chronic ethanol consumption[J].European Journal of Pharmacology,2002,442(3):241-250.
[10]张学亮.β受体阻滞剂(S)-(-)-倍他洛尔盐酸盐和(S)-(-)-美托洛尔盐酸盐的合成.华中科技大学,硕士学位论文,2008:10.
[11]李素民.咔唑心安的化学合成及其HPLC手性拆分.华中科技大学同济医学院,硕士学位论文,1996.
[12]冯涛,李佳,任晓慧,屠春燕.高效毛细管电泳分离美托洛尔对映体.分析试验室,2015,34(12):1408-1410.
[13]王伟,陈宇云,杨维平,章竹君.毛细管电泳手性分离-激光诱导荧光检测普萘洛尔对映体.分析化学,2005,(08):1113-1115.
[14]马晓伟,左莉华,徐淑英,郭兴杰.2-甲基-β-环糊精作为手性选择剂对5种药物对映体的毛细管电泳拆分研究.沈阳药科大学学报,2012,29(01):55-58.
[15]王建军,郑国钧,王佳亮,杨柳,吴襟,沙倩,孙万儒.β-受体阻滞剂及其类似物的毛细管电泳手性分离.分析化学,2001,(06):671-675.
[16]王兆昆,赵龙山,崔智,严加高,郭兴杰.磺酸化-β-环糊精为手性选择剂分离5种β-受体阻断剂类药物.沈阳药科大学学报,2015,32(12):962-966.
[17]冯颖.水相/非水相毛细管电泳中环糊精手性拆分β-受体阻滞剂机理研究.暨南大学,2015.
[18]李学仁,程庆春,杨跃伟,张云斌,尚素芬,王洪.高效毛细管电泳法研究美托洛尔、艾司洛尔和维拉帕米的对映体的手性分离.中国药学杂志,1999,(04):45-46.
[19]肖溶,杜培刚,罗月影,等.羧甲基-β-环糊精取代度对毛细管电泳手性拆分普罗帕酮和普萘洛尔对映体的影响.贵阳医学院学报,2010,35(2):144-150.
[20]吴晓苹,陈小燕,郑敏敏.毛细管电泳-安培检测法分离分析手性药物索他洛尔.分析化学,2010,38(12):1776-1780.
[21]彭佳伟,徐蕾,李小晨,等.基于离子液体辅助的毛细管电泳法手性拆分阿替洛尔对映异构体.化工时刊,2016,30(8):1-4.
[22]利健文.毛细管电泳手性拆分美托洛尔、阿普洛尔和卡替洛尔对映体.理化检验-化学分册,2010,46(2):175-177.
[23]韦寿莲,刘玲,严子军,等.鼠血中烯丙洛尔对映体的毛细管电泳分离与测定.分析测试学报,2010,29(5):488-492.
[24]王钰,杨思文,代语林,邓宁,王燕,何建波,朱燕舞.离子液体对毛细管电泳分离美托洛尔和普萘洛尔对映体的影响研究[J].药物分析杂志,2014,34(11):2091-2097.
[25]Wren S A C,Rowe R C.Theoretical aspects of chiral separation in capillary electrophoresis I,Initial evaluation of a model[J].Journal of Chromatography A,1992,(603):235-241.
[26]王益莹.正电型β-环糊精在毛细管电泳中对手性药物拆分的基础研究.南京理工大学,2015,硕士学位论文.