手性药物高效毛细管电泳拆分方法的研究进展

高效毛细管电泳法（high performance capillary electrophoresis,HPCE）在手性药物拆分领域得到了广泛的应用。目前,手性离子液体用于毛细管电泳拆分手性药物时,常与环糊精（CD）类手性选择剂构成二元体系产生协同作用,增强了手性离子液体潜在的手性拆分能力。依据对映体拆分的手性选择剂的种类及浓度、缓冲液的浓度和pH、电泳工作电压和温度,选出手性拆分的最佳条件。综述手性药物的发展以及应用HPCE拆分手性药物的文献资料,并对其研究的新进展作了分析。     

以高取代磺酸基环糊精为手性选择剂毛细管电泳法拆分4种药物对映体

目的 :采用新型高取代磺酸基环糊精为毛细管电泳手性选择剂 ,研究萘普生、酮洛芬、氧氟沙星和阿托品 4种药物的对映体分离。方法 :在毛细管电泳仪上 ,以逆向区带电泳模式 ,研究 3种高取代磺酸基环糊精手性选择剂对 4种药物对映体拆分的影响 ,优化了分离条件 ,并探讨了分离机理。结果 :在优化的条件下 ,4种药物对映体取得很好的分离结果。结论 :在毛细管电泳中 ,高取代磺酸基环糊精是一种很有潜力的手性选择剂 ,值得进一步研究。     

以高取代磺酸基环糊精为手性选择剂毛细管电泳法拆分4种药物？…

目的：采用新型高取代磺酸基环糊精为毛细管电泳手性选择剂,研究萘普生、酮洛芬、氧氟沙星和阿托品４种药物的对映体分离。方法：在毛细管电泳仪上,以逆向区带电泳模式,研究３种高取代磺酸基环糊精手性选择剂对４种药物对映体拆分的影响,优化了分离条件,并探讨了分离机理。结果：在优化的条件下,４种物对映体取得很好的分离结果。结论：在毛细管电泳中,高取代磺酸基环糊精是一种很有潜力的手性选择剂,值得进一步研究。     

纳米粒子在毛细管电泳手性药物拆分中的应用研究进展

目的阐述近年来纳米粒子在毛细管电泳手性药物拆分中的应用研究进展。方法归纳国内外最新的文献报道,对纳米粒子在毛细管电泳手性拆分领域的应用研究进展进行综述。结果纳米粒子用于毛细管电泳手性拆分,可以显著提高对映体的分离度和分离效率。结论纳米粒子因其特殊的物理化学性质,在毛细管电泳手性药物分离领域具有十分良好的发展前景。     

体内药物分析中的手性拆分方法

综述了近年来药物对映体的手性拆分方法在体内药物分析中的进展情况 ,介绍了气相色谱、高效液相色谱、毛细管电泳等方法在药物对映体拆分上的应用及其发展方向     

水溶性β-CD聚合物在毛细管电泳中分离手性药物罗格列酮和芬氟拉明

目的：建立了一种用毛细管电泳拆分罗格列酮和芬氟拉明两种药物对映体的方法。方法：以水溶性β-环糊精聚合物（β-CD polymer）为手性选择剂，采用毛细管区带电泳模式，考察了手性选择剂浓度、背景电解质溶液pH值、柱温及分离电压等因素对分离的影响。结果：在优化的实验条件下，两种药物的手性对映体均达到基线分离。结论：方法操作简单，重现性好，可用于这两种药物的质量控制。     

羧甲基-β-环糊精取代度对毛细管电泳手性拆分的影响

目的:研究羧甲基-β-环糊精取代度对毛细管电泳手性拆分影响。方法:以氯醋酸为羧甲基化试剂,通过调整物料比例合成了3种不同取代度的羧甲基-β-环糊精,并通过核磁共振直接对它们的平均取代度和取代位置进行表征;以萘哌地尔和吲哒帕胺为模型化合物,考察了不同取代度的羧甲基-β-环糊精对毛细管电泳手性拆分的影响。结果:随着羧甲基-β-环糊精取代度的增大,萘哌地尔分离随之改善;相反,吲哒帕胺对映体在较低取代度的羧甲基-β-环糊精条件下获得良好分离。结论:羧甲基-β-环糊精的取代度对毛细管电泳手性拆分和运行缓冲液的离子强度有重要影响,因此在手性分离中使用表征清晰的环糊精衍生物是至关重要的。     

坦洛新对映体的HS-β-环糊精的HPCE手性拆分研究

目的:建立坦洛新对映体的毛细管电泳手性拆分法。方法:10 mmol·L~(-1)HS-β-环糊精为手性添加剂,以25 mmol·L~(-1)的磷酸缓冲液,用三乙醇胺调节 pH 为3.0为背景电解质溶液,运行电压为-20 kV,毛细管温度为20℃,检测波长200nm,对坦洛新对映体进行手性分离研究,并考察了多种因素对分离的影响。结果:在该毛细管电泳条件下,坦洛新对映体能得到基线分离。结论:本方法简单、快捷、经济,可适用于坦洛新对映体分离和纯度检查。     

环糊精—毛细管区带电泳法分离手性药物对映体

本文综述了近年来以环糊精及其衍生物为手性选择性的毛细管区带电泳法在分离手性药物及中间体的对映体中的应用，介绍了环糊精的类型，浓度，缓冲液的ｐＨ和有机溶剂对分的分离的影响，以及关系实验手一些具体要求。     

高效毛细管电泳法拆分5种手性药物

目的:以硫酸化-β-环糊精(S-β-CD)为手性选择剂,建立毛细管电泳法分离苯丙哌林、曲马多、联苯苄唑、利阿唑和1-苄基-3哌啶醇5种对映体药物。方法:采用未涂壁熔融石英毛细管柱,磷酸二氢钠缓冲溶液,分离电压20 kV,考察了硫酸化-β-环糊精质量浓度、背景电解质pH值、缓冲盐浓度共3个因素对手性药物拆分的影响。结果:在最优的电泳条件下5种药物均达到基线分离,分离度分别为10.41,6.10,4.09,2.80,5.50。结论:所建立的方法适于苯丙哌林、曲马多、联苯苄唑、利阿唑和1-苄基-3哌啶醇的对映体分离。     

Selected fundamental aspects of chiral electromigration techniques and their application to pharmaceutical and biomedical analysis.

While capillary electrophoresis has been established as a major enantioseparation technique within the last decade, the potential of capillary electrochromatography is still studied extensively. This review summarizes recent applications of electromigration techniques with regard to the enantioseparation of chiral drugs. The first part discusses the general aspects of migration models and the enantiomer migration order. The application of capillary electrophoresis to chiral pharmaceutical analysis considers recent literature on: (1) chiral resolutions of non-racemic mixtures of enantiomers for the development of assays and the determination of the stereochemical purity of the drugs, (2) chiral separations of compounds in pharmaceutical formulations and products, and (3) enantioseparations of drugs in biological samples. A shorter section devoted to chiral electrochromatography discusses some fundamental aspects as well as the application to the chiral analysis of drugs including bioanalysis.     

Enantioselective analysis of amisulpride in pharmaceutical formulations by means of capillary electrophoresis

A capillary electrophoretic method has been developed for the enantioselective analysis of amisulpride in pharmaceutical formulations, using β-cyclodextrin sulfate as the chiral selector. Several parameters, such as cyclodextrin type and concentration, buffer concentration and pH and capillary temperature were investigated for method optimisation. Baseline enantioseparation of the racemic compound was achieved in less than 10 min using a fused silica capillary (50 μm i.d. and 33.0, 8.5 cm, total and effective length, respectively), filled with a background electrolyte consisting of a 10 mM citrate buffer at pH 3.5 supplemented with 0.22% (w/v) β-cyclodextrin sulfate at 20 °C and applying a voltage of +15 kV. Formulation analysis was carried out after analyte extraction by methanol. The method was fully validated, with good results in terms of precision, selectivity, accuracy and amount of drug found with respect to the label claim. Thus, the method seems to be suitable for the enantiomeric analysis of amisulpride in pharmaceutical formulations.     

多聚乙酰神经氨糖酸毛细管电泳拆分新药马来酸氨氯地平对映体及手性分离机制

目的将多聚乙酰神经氨糖酸用作分离双氢吡啶类药物对映体的毛细管电泳手性选择剂，建立新药马来酸氨氯地平对映体的拆分方法。方法考察了手性选择剂浓度、运行缓冲液pH值、毛细管温度、工作电压和多糖分子量等因素对手性分离的影响。结果马来酸氨氯地平两对映体得到了完全分离，分离度为2.20，并研究了多聚乙酰神经氨糖酸对马来酸氨氯地平的手性识别机理。结论本法操作简便，可用于该新药对映体的分离分析。     

Use of negatively charged cyclodextrins for the simultaneous enantioseparation of selected anesthetic drugs by capillary electrophoresis-mass spectrometry.

The simultaneous enantioseparation of selected anesthetic drugs was studied by capillary electrophoresis (CE) in presence of three different negatively charged cyclodextrins (CDs). Among the chiral selectors tested, namely carboxymethyl, sulfobutyl ether and sulfated-beta-CD, the latter appeared to be the most effective to achieve the enantiomeric resolution of the investigated compounds. Beside CD type, resolution was greatly influenced by the buffer pH, the molecular structure of the anesthetic compounds, CD concentration and temperature. The optimum electrophoretic conditions for the stereoselective analysis of the studied anesthetics were obtained with a poly(vinyl alcohol) coated capillary (48.5 cm total length x 50 microm I.D.), a 50 mM Tris-phosphate buffer at pH 2.5 containing 6 mg ml(-1) of sulfated-beta-CD, an applied voltage of 30 kV and a temperature of 30 degrees C. Under these optimized conditions, four drugs, namely bupivacaine, mepivacaine, ketamine and prilocaine, were simultaneously enantioresolved in less than 12 min. Furthermore, the method was applied to the stereoselective analysis of mepivacaine in a pharmaceutical preparation. Finally, the method was on-line coupled to electrospray ionization mass spectrometry using the counter current partial-filling technique.     

Optimization of gas chromatographic method for the enantioseparation of arylpropionic non-steroidal anti-inflammatory drug methyl esters

The gas chromatography (GC) method for enantioseparation of well-known non-steroidal anti-inflammatory drugs ibuprofen, fenoprofen and ketoprofen methyl esters mixture was developed. Best enantioseparation was performed on capillary column with heptakis-(2,3-di-O-methyl-6-O-t-butyldimethyl-silyl)-beta-cyclodextrin stationary phase and hydrogen used as a carrier gas. Initial temperature, program rate and carrier pressure were optimized to obtain best resolution between enantiomers.     

血清S-CD105监测术后复发转移性乳腺癌临床价值研究

目的探讨复发转移性乳腺癌患者血清S-CD105表达情况及其临床意义。方法用酶联免疫吸附实验（ELISA）检测50例复发转移性乳腺癌（复发转移组）,20例乳腺良性疾病（良性疾病组）及15例健康女性（健康对照组）血清S-CD105的浓度;用微粒子化学发光法检测复发转移患者同期血清癌胚抗原（CEA）、糖链抗原-3（CA15-3）的浓度。结果复发转移性乳腺癌患者血清S-CD105浓度明显高于乳腺良性疾病及健康对照（P〈0.01）。血清S-CD105表达阳性率高于CEA、CA15-3（P〈0.01）,而与CEA、CA15-3联合表达相似（P〉0.05）;S-CD105表达与复发转移部位、原肿瘤病理类型、腋淋巴结转移状况、雌激素受体（ER）、孕激素受体（PR）、人表皮生长因子受体-2（HER-2）表达及月经状况无关（P〉0.05）。结论复发转移性乳腺癌患者血清S-CD105表达明显升高。单项检测S-CD105优于CEA、CA15-3与CEA、CA15-3联合表达相似。血清S-CD105有望作为乳腺癌复发转移的一项监测指标。     

Chiral analysis of pharmaceuticals by capillary electrophoresis using antibiotics as chiral selectors

The review summarizes the use of the chiral capillary electrophoresis (CE) with different class of antibiotics as chiral selectors in the pharmaceutical field. Basic factors influencing the enantioseparation are shortly discussed. Non-aqueous capillary electrophoresis is also included as well as the coupling of CE to MS. The selection of a chiral selector according the ionic state and structure of the analyte is described. Summary of pharmaceutical applications of chiral CE is given.     

Capillary electrophoretic separation of drug enantiomers in human serum

Enantiomers of various solutes including several basic drugs and alpha-amino acids were analyzed by capillary electrophoresis in diluted human serum, and chloroquine and tryptophan were found to be well enantioseparated. In order to specify the protein responsible for enantioseparation, these drug enantiomers were analyzed in the presence of various serum protein fractions. The results indicated that albumin fraction caused enantioseparation but the alpha and beta -globulin mixed fraction, the gamma-globulin fraction and the alpha(1)-acid glycoprotein fraction did not exhibit any enantioseparation. The association constants between these drugs and albumin were roughly estimated based on our method. Approximate values were 1.50 x 10(3) and 1.85 x 10(3) M(-1) for chloroquine enantiomers, and 1.51 x 10(4) and 2.45 x 10(4) M(-1) for tryptophan enantiomers. The difference of the association constant values between the enantiomers was found to be 19% for chloroquine and 38% for tryptophan, when calculated based on the slower moving enantiomers.     

Recent results of biotransformation of drugs: investigation of the in vitro biotransformation of thalidomide using a dual cyclodextrin system in capillary electrophoresis

A previously developed capillary electrophoresis method for the simultaneous separation and enantioseparation of thalidomide (TD) and its hydroxylated metabolites was extended to one additional biotransformation product. The dual chiral selector system using native beta-cyclodextrin (beta-CD) and the negatively charged sulfobutyl-beta-CD (SBE-beta-CD) was slightly modified up to a concentration of 12 mg/ml running buffer of each CD. The carrier mode in which these buffer additives transport the neutral compounds to the detector as well as the use of a polyacrylamide-coated capillary were necessary to achieve reproducible enantioseparations of all eight analytes.     

血清S-CD105在结直肠癌中的表达及临床意义

目的探讨血清S-CD105在结直肠癌中的表达及临床意义。方法选择北京军区天津疗养院收治的经病理证实的结直肠癌35例（结直肠癌组）、结直肠息肉10例（结直肠息肉组）和健康体检者10例（对照组）,用酶联免疫吸附法（enzyme-linked immunosorbent assay,ELISA）检测血清S-CD105的浓度,观察其与临床病理指标的关系及预后。结果结直肠癌组术前S-CD105浓度均高于术后及结直肠息肉组、对照组（P〈0.05）;结直肠息肉组和对照组比较差异无统计学意义（P〉0.05）;结直肠癌组术后S-CD105浓度均低于结直肠息肉组和对照组,但差异无统计学意义（P〉0.05）。血清S-CD105浓度随着淋巴结转移、Dukes分期升高及癌组织中血管内皮生长因子（VEGF）表达增强而明显升高（P〈0.05）;术后1~3年发生远处转移的5例结直肠癌血清S-CD105浓度明显升高。结论血清SCD105表达对评价结直肠癌的预后和监测复发、转移具有重要的临床价值。