脂质体电动色谱法评价阿魏酸与生物膜的相互作用

利用脂质体与生物膜结构的相似性,将脂质体加入毛细管电泳缓冲溶液中作为假固定相,在数分钟内测定了阿魏酸的脂水分配系数Klw,建立了脂质体电动色谱评价阿魏酸与生物膜相互作用的方法。研究了脂质体中胆固醇的含量、缓冲溶液pH值和缓冲体系对Klw的影响。结果表明,在实验条件范围内(胆固醇含量0~30%,pH值4.0~12.0),胆固醇含量升高,缓冲溶液pH值增大,Klw降低;在不同的缓冲体系中,离子强度越大,Klw越大。脂水分配系数的变化反映了阿魏酸与生物膜相互作用。     

中性芳香族溶质在脂质体电动色谱中的热力学分配行为

脂质体电动色谱是一种理想的评价药物与生物膜相互作用的模型. 在288～323 K范围内测定了中性芳香族溶质在脂质体电动色谱中的分配系数, 通过三项式拟合Van't Hoff图获得了一系列的热力学参数, 研究了溶质在脂质体电动色谱中的热力学分配行为. 结果表明, 分配系数随体系温度的升高和苯环所带亚甲基数目的增加而增大. 从288到323 K, ΔH＞0, －TΔS＜0, ΔG＜0, 溶质在脂质体电动色谱中的分配过程为熵驱动过程. 从288到298 K, 脂质体电动色谱分配系统的ΔC_p为负值, 其表现行为与经典疏水作用一致. 从303到323 K, 脂质体电动色谱分配系统的ΔC_p为正值, 其表现行为与经典疏水作用不完全吻合. ΔH和ΔS呈线性关系, 该分配系统存在焓熵补偿.     

Liposome Electrokinetic Chromatography: An in vitro Approach for Predicting Ecotoxicity

Liposome electrokinetic chromatography (LEKC) is a powerful tool for the study of drug membrane interactions. An investigation of the use of the retention in LEKC as an in vitro approach to predict the ecotoxicity is proposed. The ecotoxicity parameters (LC₅₀ in fish, daphnia and mysid shrimp, EC₅₀ in green algae and daphnia, and values of chronic ecotoxicity in fish and green algae) for 15 aromatic compounds were extracted from ECOTOX database from the US Environmental Protection Agency. Quantitative retention–activity relationship (QRAR) models for the estimation of ecotoxicity were established. The r ² of the fitted linear equations ranged from 0.80 to 0.87, which suggested good correlation between the retention in LEKC and the ecotoxicity parameters. The predictive ability of the models was evaluated by cross-validation. The results obtained indicated the usefulness of the LEKC systems investigated for the rapid ecotoxicity assessment of aromatic compounds.     

用胶束毛细管电动色谱法分离三硝基甲苯异构体的研究

用胶束毛细管电动色谱法（ＭＥＫＣ）分离三硝基甲苯（ＴＮＴ）异构体。研究了背景电解质、十二烷基硫酸钠（ＳＤＳ）浓度、缓冲溶液添加剂Ｂｒｉｊ３５、ｐＨ等对分离的影响,找出了最佳分离条件,使三硝基甲苯的６种异构体在几分钟内达基线分离。     

脂质体电动色谱用于预测皮肤渗透性的定量保留活性关系的建立

脂质体电动色谱 （Liposome electrokinetic chromatography,LEKC）是一种简单快速的评价药物与生物膜相互作用的方法。本文建立了脂质体电动色谱作为高通量筛选皮肤渗透性的体外分析方法。将脂质体电动色谱中保留因子的对数值（log k）作为自变量建立了定量保留活性关系式。采用SPSS分析软件对于16种结构不同的化合物进行分析,结果表明log k与皮肤渗透性常数线性相关性良好( R²=0.886)。采用交互验证评价了该模型的预测能力。在定量保留活性关系中的一个变量和传统定量构效关系中的三个变量可解释的能力( R² =0.704)相似。文中建立的定量保留活性关系模型对于新化合物早期的筛选可提供一种有效快捷的方法。     

脂质体模拟生物膜研究药物吸收

应用膜模型脂质体研究了脂溶性药物水杨酸、水溶性药物维生素B₆和头孢曲松钠、喹诺酮类抗菌素氟哌酸及抗癌药物阿霉素的吸收,并与细胞膜上的吸收情况作了比较.吸收曲线呈直线关系的水杨酸吸收依赖被动扩散.维生素B₆的实验结果表明吸收依赖于细胞膜上的蛋白,是一种化学过程,吸收值不呈直线关系.头孢曲松钠的吸收方式是简单的扩散过程.氟哌酸在离子作用下扩散通过脂双层.阿霉素是在细胞核内核酸的牵引力作用下跨膜吸收.     

非水胶束电动色谱分离邻苯二甲酸酯类化合物

非水胶束电动色谱(NAMEKC)兼具非水毛细管电泳的优点和胶束电动色谱的分离机制,尤其适于对强疏水性化合物进行分离分析。在以甲酰胺为非水溶剂的电泳介质中,采用十二烷基硫酸钠（SDS）形成胶束相,开展NAMEKC方法的研究。通过添加水溶液、调节水溶液酸度、添加有机溶剂、改变SDS浓度等操作条件的考察,在15 min 内实现了3种美国环保局优先监测的污染物——邻苯二甲酸二甲酯、邻苯二甲酸二乙酯、邻苯二甲酸二丁酯的分离。分离度最小者为1.5,检测限优于3.04 mmol/L(以信噪比为3计)。3种典型的强疏水性物质的成功分离,显示出NAMEKC方法在分离疏水性物质方面的优势,扩展了NAMEKC在电中性有机物分析中的应用。     

微乳电动毛细管色谱分离分析氟喹诺酮类药物

建立了一种同时分离7种氟喹诺酮类药物(FQs)的微乳液电动毛细管色谱(MEEKC)。用十二烷基硫酸钠(SDS)作为表面活性剂,系统考察了缓冲溶液浓度和pH、SDS、助表面活性剂和油相的浓度、温度等对分离的影响。最佳分离条件为:1%正庚烷(V/V),100mmol/LSDS,10%正丁醇(V/V)和8mmol/L磷酸盐-四硼酸钠缓冲溶液(pH7.30)。以氧氟沙星(OF)作内标,FQs标准水溶液和标准血清溶液的线性范围分别为1.2×10-6~5.0×10-4mol/L和2.0×10-6~5.0×10-4mol/L,检出限(S/N=3)均为9.7×10-7mol/L。方法直接应用于滴眼液中环丙沙星(CPF)的测定,精密度和准确度高;应用于血液中加替沙星(GTF)的测定涉及固相萃取预处理样品,萃取平均回收率为90.6%,日内、日间精密度分别为3.3%和3.6%,结果满意。     

Chiral Separations by Ligand-Exchange Micellar Electrokinetic

The separation of enantiomers is of great importance in biology, pharmaceutics, agriculture and environment. The different separation modes ( i. e. capillary zone electrophoresis ( CZE ), micellar electrokinetic chromatography ( MEKC ), capillary electrochromatography ( CEC ), etc )     

Study of Tea Digitized Chromatographic Fingerprint Spectra Using Micellar Electrokinetic Chromatography

IntroductionTeaisthemostwidelyconsumedbeverageinpeople’slife .Theheightenedpopularityofthisbeveragethroughouttheworldinrecentyearsmaybedueinparttotheevidenceofarelationshipbetweenteaconsumptionandpreventionofcertainformsofhumandisease .Themaincomponentsofteaarepolyphenoliccompounds ,commonlyknownascatechins ,whichrepresentagroupofcom poundsbelongingtotheflavonoidfamily .Thesecom poundsarewidelydistributedinthetealeavesandconsti tuteupto 30 %ofthedryleafweight.1Muchinteresthasbeenfocusedoncat…     

环糊精修饰毛细管胶束电动色谱同时分离检测橙皮苷和柚皮苷对映体

本文利用环糊精修饰毛细管胶束电动色谱法(CD-MEKC)同时分离检测橙皮苷和柚皮苷对映体。实验优化的条件为:以60mmol/L胆酸钠(SC)+30mmol/L羟丙基-β-环糊精(HP-β-CD)+20 mmol/L NaH2PO4-100 mmol/L NaOH(pH=9.0,97%(V/V))+3%(V/V)甲醇为运行缓冲液,分离电压25kV,紫外检测波长214nm。在上述最佳条件下,橙皮苷和柚皮苷对映体在9min内得到完全分离,橙皮苷对映体的检测限(S/N=3)分别为0.13μg/mL和0.25μg/mL;柚皮苷对映体的检测限(S/N=3)分别为0.14μg/mL和0.07μg/mL。将所建立的方法用于胃苏颗粒制剂中橙皮苷和柚皮苷的对映体测定,回收率在86.0%~113.2%之间。     

微乳电动色谱法的研究进展

微乳电动色谱(MEEKC)是一种以微乳为背景电解质,以电压为驱动力的分离技术。本文对MEEKC中的各调节参数进行了概述,重点归纳了MEEKC法在正辛醇-水分配系数测定、中药和手性化合物分离方面的应用,以及在操作技术上的新进展,如多路进样技术以及在线联用质谱检测技术等,并通过对相关文献的分析,对一直存有争议的MEEKC与胶束电动色谱(MEKC)的联系与区别进行了讨论,最后提出了MEEKC法未来的发展空间。     

SDS-Based Biomembrane Mimetic Chromatography for Prediction of Human Drug Transport as an in Vitro Technique

The main oral drug absorption barriers are fluid cell membranes, and generally drugs are absorbed by a passive diffusion mechanism. On the other hand, the blood–brain barrier (BBB) is considered to be the main barrier to drug transport into the central nervous system (CNS). The BBB restricts the passive diffusion of many drugs from blood to brain. Biopartitioning micellar chromatography (BMC), a mode of micellar liquid chromatography that uses micellar mobile phases in adequate experimental conditions, can be useful as an in vitro system in mimicking the drug partitioning process into biological systems. In this study, relationships between the BMC retention data of a heterogeneous set of 12 drugs and their pharmacokinetics parameters (human oral drug absorption and BBB penetration ability) are studied and the predictive ability of the models is evaluated. Modeling of log k _BMC of these compounds was established by multiple linear regression in two different concentrations (0.07 and 0.09 M) of sodium dodecyl sulfate (SDS). The results showed a fair correlation between human oral drug absorption and BMC retention data in 0.09 M SDS (R ² = 0.864) and a good correlation between the blood–brain distribution coefficient and BMC retention data in 0.07 M of SDS (R ² = 0.887). Application of the developed models to a prediction set demonstrated that the model is also reliable with good predictive accuracy. The external and internal validation results showed that the predicted values are in good agreement with the experimental value.     

Determination of Kynurenine and Tryptophan in Human Plasma by Stacking-Micellar Electrokinetic Chromatography

Kynurenine and tryptophan are important biomarkers for disorders in nervous and immune systems, while the low content of kynurenine in human plasma makes the determination by routine approaches difficult. In this work, an on-line preconcentration method for capillary electrophoresis was developed for the quantification of kynurenine and tryptophan. A concomitant sweeping phenomenon was observed due to the combination of micellar electrokinetic chromatography and stacking. The poor sensitivity in capillary electrophoresis was improved so that the determination of low concentrations of kynurenine became possible. Parameters that may affect the efficiency of the on-line concentration were systematically investigated and optimized. A large volume sample injection was employed for sampling at 100 mbar for 112 sec. A voltage of ?20 kV was applied, and the ionic sample matrix was removed with stacking while analytes were kept in the capillary. The voltage was switched to +18 kV and micellar electrokinetic chromatography was performed for separation and determination of kynurenine and tryptophan. Based on peak heights, the concentration factors for kynurenine and tryptophan were 33 and 31, respectively. The analytical performance of the established method was studied; good linearity of kynurenine was observed in the range of 0.3–30 µM (R² = 0.9988), and 0.3–60 µM (R² = 0.9963) was obtained for tryptophan. LODs of 0.15 µM for kynurenine and 0.30 µM for tryptophan were obtained. The optimum method was successfully tested in human plasma; kynurenine and tryptophan were well identified, which suggests that this method has potential for the analysis of biological samples.     

SDS-Based Biomembrane Mimetic Chromatography for Prediction of Human Drug Transport as an in Vitro Technique

The main oral drug absorption barriers are fluid cell membranes, and generally drugs are absorbed by a passive diffusion mechanism. On the other hand, the blood–brain barrier (BBB) is considered to be the main barrier to drug transport into the central nervous system (CNS). The BBB restricts the passive diffusion of many drugs from blood to brain. Biopartitioning micellar chromatography (BMC), a mode of micellar liquid chromatography that uses micellar mobile phases in adequate experimental conditions, can be useful as an in vitro system in mimicking the drug partitioning process into biological systems. In this study, relationships between the BMC retention data of a heterogeneous set of 12 drugs and their pharmacokinetics parameters (human oral drug absorption and BBB penetration ability) are studied and the predictive ability of the models is evaluated. Modeling of log k _BMC of these compounds was established by multiple linear regression in two different concentrations (0.07 and 0.09 M) of sodium dodecyl sulfate (SDS). The results showed a fair correlation between human oral drug absorption and BMC retention data in 0.09 M SDS (R ² = 0.864) and a good correlation between the blood–brain distribution coefficient and BMC retention data in 0.07 M of SDS (R ² = 0.887). Application of the developed models to a prediction set demonstrated that the model is also reliable with good predictive accuracy. The external and internal validation results showed that the predicted values are in good agreement with the experimental value.

     

Enantiomeric Separation of Two Antiparkinsonian Drugs by Electrokinetic Chromatography Using Dextran Sulfate

Anionic polysaccharide dextran sulfate (DxS) was successfully employed as chiral selector for the enantioseparation of two antiparkinsonian drugs, including rotigotine and trihexyphenidyl (THP), by electrokinetic chromatography (EKC). The enantioseparation was performed under normal and reversed polarity modes and reversed enantiomer migration order was achieved under two modes. The parameters affecting the chiral separation, such as buffer pH, DxS concentration, organic additive, and temperature were investigated and optimized. Reversed polarity mode provided better separation for the two drugs. The optimized conditions for the enantioseparation under reversed polarity mode were 2.0% (w/v) DxS, 10 mM phosphate buffer, pH 2.5 with an applied voltage of ?30 kV at 25 °C. Direct UV detection was performed at 200 nm. Under the optimal conditions, rotigotine and THP enantiomers were enantioresolved in 40 min with the resolution of 2.0 and 5.8, respectively. The analytes could be enantioseparated using DxS of molecular mass 1,000,000 or 500,000. It was inferred that the electrostatic, hydrophobic, and steric interactions may be involved in the chiral separation mechanism in this study.     

Determination of s-Triazine Herbicides by Micellar Electrokinetic Chromatography Using Sodium Dodecyl Sulfate

It was shown that Simazine, Atrazine, Propazine, and Prometryne can be separated by micellar electrokinetic chromatography using sodium dodecyl sulfate as a micelle-forming agent. The detection limits were found to be 0.1 mg/L for Simazine and 0.05 mg/L for Atrazine, Propazine, and Prometryne at a signal-to-noise ratio of 2 in a buffer electrolyte containing 10 mM sodium tetraborate and 30 mM sodium dodecyl sulfate. The time of separation was 12 min.     

胶束电动毛细管色谱检测鱼肉中的七种生物胺

建立了一种利用胶束电动毛细管色谱同时检测鱼肉中组胺、腐胺、2-苯乙基胺、尸胺、色胺、亚精胺及精胺7种生物胺的方法。样品经6%过氯酸萃取后,由苯甲酰氯衍生化,以含0.06 mol/L脱氧胆酸钠的0.02 mol/L硼酸(pH 9.2)-甲醇(体积比为95∶5)混合液为电泳介质,电泳电压25 kV,温度25 ℃,检测波长214 nm,在12 min内实现了7种生物胺的完全分离。7种生物胺的浓度与其峰面积在一定的范围呈良好的线性关系,检出限除组胺为15 μg/g外,其余均为5 μg/g。迁移时间和峰面积的日内、日间相对标准偏差均小于5%。该法用于海鱼中7种胺类物质含量的测定,结果令人满意。     

模拟生物膜色谱用于预测药物的小肠吸收

采用涂敷磷脂的硅胶为模拟生物膜色谱固定相,与传统的凝胶体相比固定相的机械强度及磷脂固载能力均有较大提高,且有较好的稳定性。研究发现氢化可的松等6种药物在模拟生物膜色谱上pH5.4、pH7.0及pH7.4三种缓冲环境下的色谱保留值迭加的结果能够与药物的肠吸收指数押送好的拟合,线性相关系数为0.9365,该结果高于单一pH条件下拟合结果,并将此结果与药物在C18反相色谱上的保留值及辛醇-水系统下的分配系数与药物的小肠吸收的拟合结果进行比较,表明与这两种模型相比模拟生物膜色谱预测药物的小肠吸收有更高的准确度。     

阳离子表面活性剂胶束电动毛细管色谱中的假峰现象

研究了以十六烷基三甲基溴化铵为准固定相的胶束电动毛细管色谱中假峰的起源。指出在一定条件下,一个组分可能出现两个峰。实验表明,被分析物双峰的相对峰面积取决于被分析物与表面活性剂反应的时间、温度以及表面活性剂在样品中的浓度。这意味着被分析物与表面活性剂之间的反应是一个慢过程,这种相互作用能够产生一种稳定的物质,并导致假峰的形成。根据实验结果,溶质与胶束之间的快速相互作用机理应被质疑。