制备手性色谱拆分氧氟沙星光学异构体

利用配合交换原理,采用手性流动相添加剂方法,在反相高效液相色谱（ＲＰ－ＨＰＬＣ）制备柱上,拆分了氧氟沙星的两种对映体。流动相组成为手性添加剂溶液（含６ｍｍｏｌ／ＬＬ－苯丙氨酸和３ｍｍｏｌ／ＬＣｕＳＯ４）－ＣＨ３ＯＨ（８４：１６）,流速４．６ｍＬ／ｍｉｎ,紫外检测波长２９３ｎｍ。经提取纯化后,确证首先洗脱的是Ｓ－（＋）－氧氟沙星,后一个洗脱的是Ｒ－（＋）－氧氟沙星。经对映体选择性分析方法测定,制备获得的两种对映体的光学纯度均大于９９％。     

直链淀粉手性固定相拆分联二萘酚对映体

建立了联二萘酚对映体的高效液相色谱拆分方法。使用ChiralpakAD-H手性色谱柱,考察了流动相中极性调节剂的种类和比例、柱温以及流速对拆分联二萘酚对映体的影响。确定了最佳拆分条件:流动相为V(正己烷):V(乙醇)=55:45;流速为0.8mL/min;检测波长254nm;柱温30℃。计算了联二萘酚与固定相相互作用的焓变差值Δ(ΔH0)和熵变差值Δ(ΔS0)分别为-2.10kJ/mol和-4.94J/(mol.K),并考察了在以乙醇或异丙醇为极性调节剂流动相中两对映体的出峰顺序,结果发现在这两种流动相中出峰顺序是相反的。方法可用于联二萘酚的手性分离与检测。     

2,2,2-三氟-1-(9-蒽基)乙醇对映体在涂敷型手性固定相上的拆分

用高效液相色谱法在涂敷１５％（Ｗｔ）三苯基氨基甲酸纤维素醌手性柱上,考察了洗脱液正己烷／醇（Ｖ／Ｖ）中醇对分离－２,２,２－三氟－１（９－蒽基）乙醇对映体的影响,初步认为,在对映体分离过程中,洗脱液中醇与手性固定相的ＮＨ和Ｃ＝Ｏ形成氢键作用,此过程与对映体和手性固定相的ＮＨ和Ｃ＝Ｏ所形成氢键作用相竞争;洗脱液中醇的结构不同之所以影响对映体的分离效果,还与洗脱中醇改变固定相中手性空穴的立体环境有关,     

高效液相色谱手性流动相法拆分甲状腺素对映体

运用高效液相色谱手性流动相法（ＨＰＬＣ－ＣＭＰ）对影响甲状腺素对映体（Ｄ－,Ｌ－Ｔ４）分离方法的因素：三乙胺（ＴＥＡ）浓度,流动相ｐＨ值,铜离子（Ｃｕ２＋）浓度,Ｌ－脯氨酸（Ｌ－ｐｒｏ）浓度,柱温以及流动相的流速进行了系统的研究。同时,考察了色谱方法分离Ｔ４对映体的线性关系,精密度和准确度。线性响应范围为０．６～３．２　ｎｍｏｌ　（Ｄ－,Ｌ－Ｔ４）,线性相关系数为ｒＤ－Ｔ４＝０．９９８０,ｒＬ－Ｔ４＝０．９９９０,日内和日间的精密度分别为ＲＳＤ＜２．３％（ｎ＝６）,ＲＳＤ＜３．１５％（ｎ＝５）。结果表明本实验所得的色谱条件较文献报道的优越,分离条件简单,重现性好。ＨＰＬＣ－ＣＭＰ法测定甲状腺素对映体其意义在于该方法可为定量测定药品及人体血液中Ｄ－,Ｌ－Ｔ４两种异构体,为治疗药物监测（ＴＤＭ）和药物不良反应监测（ＡＤＲｓ）提供了依据。     

Pirkle型手性固定相拆分盐酸克伦特罗对映体

建立并优化了高效液相色谱手性固定相分离盐酸克伦特罗对映体的方法。使用两种Pirkle型手性固定相(α-Burke-2和Pirkle-1J)拆分了盐酸克伦特罗对映体,考察了缓冲盐添加剂,有机溶剂种类和浓度,以及柱温对保留行为和分离的影响。当流动相为二氯甲烷-乙醇(19:1,V/V)含5 mmol/L乙酸铵,流速2.0 mL/min,柱温20℃时,盐酸克伦特罗对映体在α-Burke-2色谱柱上能实现较好的分离,分离度可达1.85;在Pirkle-1J色谱柱上,分离度可达0.64。盐酸克伦特罗对映体与Pirkle型固定相之间的π-π主客体相互作用和氢键作用是实现对映体分离的最主要分离机制。方法可用于盐酸克伦特罗对映体的质量控制及立体选择性药代动力学的研究。     

直链淀粉手性固定相高效液相色谱法拆分比索洛尔对映体

采用直链淀粉手性固定相高效液相色谱法在正相条件下直接拆分了比索洛尔对映异构体。分别以异丙醇、乙醇为有机改性剂,考察了流动相的组成与配比、流速及柱温等因素对比索洛尔对映体分离的影响。确定了比索洛尔对映体的最佳拆分条件:流动相正己烷-乙醇-二乙胺(体积比为88∶12∶0.1),流速0.6 mL/min,检测波长270 nm,柱温20 ℃。该方法可快捷、简便地拆分比索洛尔对映体。     

二乙酰酒石酸酐柱前手性衍生化反相高效液相色谱法拆分心得安对映体

以（Ｒ，Ｒ）－Ｏ，Ｏ－二乙酰基酒石酸酐作柱前手性衍生化试剂，用ＯＤＳ柱拆分了心得安对映体，探讨了衍生化反应条件，研究了ＰＨ及流动相组成对色谱保留行为的影响，发现心得安的两种非对映异构体衍生物的荧光响应有显著差别，对心得安对映体的半制备色谱拆分规律作了新的探讨，确定用Ｓｈｉｍ－ｐａｃｋＣＬＣ－ＯＤＳ柱进行半制备色谱拆分的最佳条件，得到的光学异构体纯度在９９％以上。     

纤维素键合手性固定相拆分6种萘满酮衍生物对映体

使用Chiralpak IC（纤维素-三（3,5-二氯苯基氨基甲酸酯）共价键合硅胶）手性柱,建立了采用手性固定相高效液相色谱拆分6种 α -芳基萘满酮类衍生物对映体的方法。考察了流动相中有机改性剂的种类和比例、柱温和流速对对映体分离的影响。结果显示6种化合物在异丙醇为改性剂的条件下均可获得较高的对映体分离度。热力学研究表明6种化合物对映体的手性拆分过程均受焓驱动影响,且低温有利于对映体分离。最终推荐分离化合物Ⅰ对映体的流动相是正己烷-异丙醇（90：10,v/v）;分离化合物Ⅱ、Ⅲ、Ⅳ对映体的流动相是正己烷-异丙醇（99：1,v/v）;分离化合物Ⅴ对映体的流动相是正己烷-异丙醇（85：15,v/v）;分离化合物Ⅵ对映体的流动相是正己烷-异丙醇（80：20,v/v）。柱温为25℃,流速为1.0 mL/min。6种化合物对映体均可在Chiralpak IC手性固定相上得到完全分离,证明该色谱柱对6种化合物具有较高的对映体选择性。     

α-苯乙醇对映体在涂敷三苯甲酸纤维素酯手性固定相上的高效液相色谱法分离──洗脱液中醇的影响

在涂敷质量分数为15％的三苯甲酸纤维素酯手性柱上,考察了洗脱液中乙醇、正丙醇、异丙醇、正丁醇体积分数在色谱分离对映体性能方面的影响。初步认为在分离过程中,洗脱液中的醇与固定相的C＝O形成氢键作用,该作用和对映体与固定相的C＝O形成的氢键作用相竞争;洗脱液中醇的结构不同之所以会影响对映体的分离效果,与洗脱液中醇改变固定相中手性空穴的立体环境有关,醇的结构不同,造成固定相中手性空穴的立体环境不同。     

α-苯乙醇对映体在涂敷三苯甲酸纤维素酯手性固定相上的高效液相色谱法分离──洗脱液中醇的影响

 在涂敷质量分数为15％的三苯甲酸纤维素酯手性柱上,考察了洗脱液中乙醇、正丙醇、异丙醇、正丁醇体积分数在色谱分离对映体性能方面的影响。初步认为在分离过程中,洗脱液中的醇与固定相的C＝O形成氢键作用,该作用和对映体与固定相的C＝O形成的氢键作用相竞争;洗脱液中醇的结构不同之所以会影响对映体的分离效果,与洗脱液中醇改变固定相中手性空穴的立体环境有关,醇的结构不同,造成固定相中手性空穴的立体环境不同。     

Preparation of a new chiral stationary phase for HPLC based on the (R)- 1-phenyl-2-(4-methylphenyl)ethylamine amide derivative of (S)-valine and 2-chloro-3,5-dinitrobenzoic acid: enantioseparation of amino acid derivatives and pyrethroid insecticides

A novel chiral stationary phase (CSP) for HPLC was prepared by bonding (R)-1-phenyl-2-(4-methylphenyl)ethylamine amide derivative of (S)-valine to aminopropyl silica gel through a 2-amino-3,5-dinitro-1-carboxamido-benzene unit. The CSP was used for the separation of some amino acid derivatives and pyrethroid insecticides by chiral HPLC. Satisfactory baseline separation required optimization of the variables of mobile phase composition. Use of dichloromethane as modifier in the mobile phase gave baseline separations of amino acid derivatives. The two enantiomers of fenpropathrin and four stereoisomers of fenvalerate were baseline separated using hexane-dichloromethane-ethanol as mobile phase. The results show that the enantioselectivity of the new CSP is better than Pirkle type 1-A column for these compounds. Only partial separations were observed for the stereoisomers of cypermethrin and cyfluthrin, which gave even and eight peaks, respectively.     

Enantiomeric separations of chiral polychlorinated biphenyls on three polysaccharide-type chiral stationary phases by supercritical fluid chromatography

Enantiomeric separations of 18 chiral polychlorinated biphenyls (PCBs) were investigated on three polysaccharide-type chiral stationary phases (CSPs; Sino-Chiral OJ, Chiralpak IB, and Chiralcel OD) by supercritical fluid chromatography (SFC). With these commonly used polysaccharide CSPs, 17 PCBs except PCB 135 (R(S) = 0.81) were well resolved (R(S) > 1.5) under appropriate mobile phases and temperatures. Using Sino-Chiral OJ, 14 PCBs could be baseline-separated, while only one and nine PCBs could be completely separated using Chiralpak IB and Chiralcel OD, respectively. The influence of column temperature was studied for the optimization of resolution, as well as for the type and percentage of organic modifier in the mobile phase. The resolution decreased as the temperature increased in the range of 26-40 °C in which the enantiomeric separations were an enthalpy-driven process. The addition of modifiers in the mobile phase decreased the resolution of the PCB enantiomers, but it clearly shortened their retention time. These separation results indicate that SFC is a promising chromatographic technique for chiral separation and enantiopure standard preparation.     

微径高效液相色谱法分离三唑类手性化合物的对映体

 采用微径高效液相色谱技术在手性纤维素色谱柱上分离了一系列 1 1,2 ,4 三唑类手性化合物。比较了微径液相色谱与传统液相色谱的分离结果 ,研究了化合物的苯环上不同取代基及取代基位置对分离的影响 ,并探讨了分离机理。     

Influence of Mobile Phase Composition on the Enantioseparation of Methoxyl Flavanones with Self-prepared CDMPC Column and Chiral Recognition Mechanism

Chiral stationary phases (CSPs) based on the cellulose derivatives have proven to be one type of the most useful CSPs in high-performance liquid chromatography because of their versatility, durability and loadability1, 2. Flavanone was often used as a standard chiral compound for evaluating cellulose derivative for chiral columns1, 3. Krause and Galensa4 reported the enantioseparation of flavanone and its seven derivatives on six kinds of commercial chiral column. 4-Methoxyl flavanone, 5-…     

Enantiomer separation by CEC

Three chiral compounds were successfully separated in a short time with two enantiomer separation models on packed-capillary electrochromatography (CEC). (i) 75 μm I.D. capillaries were packed with 5 μm β-cyclodextrin (βCD) chiral stationary phase (CSP). Effects of voltage, pH and concentration of organic modifier on electroosmotic flow (EOF) and chiral separations were investigated systematically. Enantiomers of a neutral compound (benzoin) and a neutral drug (mephenytoin) were separated within a short time with high efficiency. Efficiency of 32 000 theoretical plates per meter and resolution (R8) of 1.42 were achieved for enantiomers of benzoin using a βCD packed column with 6.2crn packed length. Efficiency of 45 000 theoretical plates per meter andR8 of 3.40 were obtained for enantiomers of mephenytoin. Especially, the enantiomer separation of mephenytion was performed in just 3.4 min with R₈ of 2.60. (ii) 75 μm I.D. capillary was packed with octadecylsilica particles (ODs). Chiral separation of a basic drug, propranolol, was studied with chiral agent, via addition of the dimethyl-β-cyclodextrin (DM β-CD) directly into the mobile phase on this column. Baseline separation and efficiency of 81 000 theoretical plates per meter were achieved for propranolol. Project supported by the Natural Science Foundation of Liaoning Province, China, the National Natural Science Foundation of China (Grant No.29875030), and the Excellent Young Scientist Award from the National Natural Science Foundation of China. (Grant No.29725512).     

CDMPC手性固定相对新型金属簇化合物的手性拆分

应用纤维素三（3,5-二甲基苯基氨基甲酸酯）（cellulose tris (3, 5- dimethylphenylcarbamate,CDMPC）手性固定相对两种新型金属簇合物进行了拆分,通过流动相组成、流速和样品溶剂等条件对拆分影响的考察进行了拆分条件的优化。实验结果表明,簇合物1和簇合物2分别在含乙醇V(hexane)∶V(ethanol)=95∶5)和异丙醇(V(hexane)∶V(2-propanol)=90∶10)的流动相中得到了较好的拆分,将样品溶解在和流动相组成相近的溶剂中更利于簇合物拆分,簇合物配体结构对簇合物在固定相上的保留和拆分有重要的影响。 在优化条件下,2种金属簇合物分离度均达到1.5以上。     

A comparison of the direct and indirect LC methods for separating enantiomers of unusual glycine and alanine amino acid analogues

Summary Reversed-phase high-performance liquid chromatographic methods were developed for the separation of the enantiomers of five glycine and twelve alanine analogues. The enantioselective separation involved two methods. The direct separations were performed on chiral stationary phases containing a macrocyclic glycopeptide antibiotic: teicoplanin (Chirobiotic T column), ristocetin A (Chirobiotic R column) or chiral crown ether (Crownpak CR(+) column). The indirect methods involved pre-column derivatization with the chiral derivatizing agents 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl isothiocyanate andN-α-(2,4-dinitro-5-fluorophenyl)-L-alaninamide (Marfey's reagent). The different methods were compared in systematic chromatographic examinations. The effects of organic modifier content, mobile phase composition, pH and flow rate on the separation were investigated. Presented at Balaton Symposium '01 on High-Performance Separation Methods, Siófok, Hungary, September 2–4, 2001     

手性金属-有机骨架[Cu_3(HL)_2(L)_2(bpy)_3]·4H_2O用于高效液相色谱拆分手性化合物

手性金属-有机骨架材料(MOFs)作为一种新型多孔材料,由于具有比表面积大、结构多样、孔尺寸可调和化学稳定性良好等特点,而备受色谱分离领域的关注。该文以(1R,2R)-1,2-环己烷二甲酸(H2L)和4,4'-联吡啶(bpy)为配体与铜离子反应,通过溶剂热法合成了一种具有二维手性网状结构的手性MOF[Cu_3(HL)_2(L)_2(bpy)_3]·4H_2O。将该手性MOF作为手性固定相制备了高效液相色谱柱。为了考察MOF[Cu_3(HL)_2(L)_2(bpy)_3]·4H_2O的手性识别能力,在正相色谱(流动相:正己烷-异丙醇)条件下,对一系列外消旋化合物在手性MOF柱上进行了拆分。该手性MOF柱对醇类、酮类、酸类、环氧化合物和醚类等10种手性化合物表现出较好的拆分效果。对该手性MOF柱的重现性、稳定性作了评价,考察了进样量对分离效果的影响,结果表明该手性MOF柱具有较好的重现性和稳定性。     

CDMPC手性固定相对金属簇化合物的手性拆分

应用纤维素三(3,5-二甲基苯基氨基甲酸酯)(CDMPC)手性固定相对2种羰基钌金属簇合物进行了拆分,通过流动相组成、流速和样品溶剂等条件对拆分影响的考察对拆分条件进行了优化。实验结果表明,簇合物1和簇合物2分别在含乙醇(V(hexane):V(ethanol)=95:5)和异丙醇(V(hexane):V(2-propanol)=90:10)的流动相中得到了较好的拆分,将样品溶解在和流动相组成相近的溶剂中更利于簇合物拆分,簇合物配体结构对簇合物在固定相上的保留和拆分有重要的影响。在优化条件下,2种金属簇合物分离度均达到1.5以上。     

Separation of the enantiomers of substituted dihydrofurocoumarins by HPLC using macrocyclic glycopeptide chiral stationary phases

Enantiomer separations by HPLC using the macrocyclic glycopeptides teicoplanin (Chirobiotic T), teicoplanin aglycon (Chirobiotic TAG), and ristocetin A (Chirobiotic R) chiral stationary phases (CSP) have been achieved on a unique series of potentially biologically active racemic analogues of dihydrofurocoumarin. The macrocyclic glycopeptides have proven to be very selective for this class of compound. All of the 28 chiral analogues examined afforded baseline separation on at least one of the macrocyclic glycopeptide CSP. The teicoplanin CSP showed the broadest enantioselectivity with 24 of the compounds baseline separated. The TAG and the R CSP produced 23 and 14 baseline separations respectively. All three mobile phase modes, i.e. normal phase (NP), reversed phase (RP), and new polar organic modes (PO), have been evaluated. The NP mode proved to be most effective for the separation of chiral dihydrofurocoumarins on all CSP tested. In the reversed phase (RP) mode, all three CSP separated a similar number of compounds. It was observed that the structural characteristics of the analytes and steric effects are very important factors leading to chiral recognition. Hydrogen bonding was found to play a secondary role in chiral discrimination in the normal phase and polar organic modes. Hydrophobic interactions are important for chiral separation in the reversed-phase mode. Chromatographic retention data does not provide information on the absolute configuration of these chiral dihydrofurocoumarin derivatives. However, when coupled with circular dichroism using the exciton coupling chirality method, the enantiomer elution order and the absolute configuration of some chiral dihydrofurocoumarins were successfully determined.