应用BMC理论方法预测选择性钙通道阻断剂药理学参数

The usefulness of biopartitioning micellar chromatography （BMC） for predicting oral drug acute toxicity and apparent bioavailability was demonstrated. A logarithmic model （an LD50 model） and the second order polynomial models （apparent bioavailability model） have been obtained using the retention data of the selective calcium channel blockers to predict pharmacological properties of compounds. The use of BMC is simple, reproducible and can provide key information about the acute toxicity and transport properties of new compounds during the drug discovery process.     

胶束电动色谱分离5种二氢吡啶类钙拮抗剂

应用胶束电动毛细管色谱,以４０ｍｍｏｌ／Ｌ硼砂－４０ｍｍｏｌ／Ｌ十二烷基硫酸钠（ＳＤＳ）为运行缓冲溶液,柱温６０℃,在１３ｍｉｎ内分离了５种二氢吡啶类钙拮抗剂药物。讨论了它ＳＤＳ浓度、硼砂浓度、缓冲溶液ＰＨ、柱温对迁移时间和分离的影响。     

Profiling of Permeable Compounds in Ligusticum chuanxiong by Biopartitioning Micellar Chromatography

The potential of biopartitioning micellar chromatography (BMC) for screening and analysis of traditional Chinese medicines (TCM) for permeable compounds has been investigated by chromatography of methanolic extracts of Ligusticum chuanxiong, as example. Six other ordinary TCM were also studied. Results showed that more than ten components of Ligusticum chuanxiong extract are significantly retained in BMC. According to relationships between retention in BMC and oral drug absorption, cell-membrane permeability, and blood–brain barrier permeability, the cell-membrane permeability and absorption properties of the permeable components of Ligusticum chuanxiong extract could be predicted from their retention in BMC. Effects on the chromatography of components of Ligusticum chuanxiong methanolic extracts of column temperature, mobile phase pH, and concentration of Brij 35 in the mobile phase are also discussed.     

双工作电极-双通道胶束电动毛细管色谱电化学法同时检测4种钙通道阻滞剂

建立了4种钙通道阻滞剂(硝苯地平、尼群地平、尼莫地平和尼卡地平)的双通道胶束电动毛细管色谱电化学检测的分析新方法。采用双工作电极和两台伏安仪,将样品的检测电位分别设定在氧化(1．0V)和还原电位(-1．0V)(vs．SCE),在一个检测池中同时获得4种样品的氧化和还原信息;采用胶束毛细管电色谱法,以硼砂(Na2B4O7)-硼酸(H3BO3)为背景电解质,同时加入十二烷基硫酸钠(SDS)和乙腈组成运行电泳介质,通过优化工作电极、检测电位、缓冲溶液、SDS浓度和乙腈等实验参数,较好地实现了4种钙通道阻滞剂的分离;将该法应用于血药浓度的测定,取得了满意的结果。     

Quantitative Structure-Retention Relationship Studies with Biopartitioning Micellar Chromatography Systems by Amended Linear Solvation Energy Relationships in Consideration of Electronic Factor

Linear solvation energy relationship (LSER) amended by the introduction of a molecular electronic factor was employed to establish quantitative structure-retention relationship of biopartitioning micellar chromatography (BMC) system. The chromatographic indices, log k, were determined by LC on a C18 column for sixty-five structurally diverse compounds, including neutral (32), acidic (19) and basic (14) compounds. Two micellar mobile phases composed of 0.04 mol L^?1 polyoxyethylene (23) lauryl ether (Brij35) were adjusted by phosphate buffer to pH 7.4 and pH 6.5, respectively. When the mean net charge per molecule (δ) was introduced into LSER as the sixth variable, the LSER regression coefficients and predictive capability were significantly improved. However, the δ coefficients of the amended LSER were quite different for acidic and basic compounds, indicating that the molecular electronic factor had a markedly different impact on the retention of acidic and basic compounds in the studied BMC system. This may attribute to the extra interaction for ionized compounds with the free silanol groups in the stationary phase. The comparison of calculated and experimental retention indices suggested that the amended LSER could reproduce adequately the retention of the structurally diverse solutes investigated in BMC.     

Selective Determination of Harmol by Room-Temperature Phosphorimetry: A Comparative Performance with Micellar Electrokinetic Capillary Chromatography

Abstract

Selective determination of harmol in the presence of other β-carboline alkaloids without the need for previous separation of components was achieved by Solid Surface Room-Temperature Phosphorimetry (SSRTP) using HgCl₂. Detection of harmol at concentrations as low as 5.2 × 10^?7 mol L^?1 can be made in urine samples. Recovery of 100±12% was achieved. The analytical performance of SSRTP was compared to Micellar Electrokinetic Capillary Chromatography (MECC).     

阴离子选择性耗尽进样-胶束扫集毛细管电泳法对痕量醋酸氢化可的松的测定

联用阴离子选择性耗尽进样和胶束扫集两种在线富集技术,建立了胶束毛细管电泳方法测定化妆品中醋酸氢化可的松的方法。讨论了SDS浓度、样品基体、进样电压、进水时间和进样时间对富集和分离的影响。优化的实验条件:以120 mmol/L SDS-20 mmol/L NaH2PO4(pH2.2)-10%(体积分数)甲醇为缓冲体系,分离电压-20 kV,进样电压-20 kV,进样时间80 s,进水时间200 s,测量波长250 nm。在该实验条件下,醋酸氢化可的松的富集倍数比普通毛细管电泳法提高了约173倍。方法的线性范围为0.05~5.0 mg/L,检出限为12.6μg/L。该方法用于化妆品中醋酸氢化可的松含量的测定,回收率为98%~105%,相对标准偏差均小于4.0%(n=4)。     

毛细管胶束电动色谱在扁桃酸合成中的应用

扁桃酸是药物中间体,可以苯甲醛为原料在相转移催化剂作用下合成制得.为了选择最佳合成条件,提高扁桃酸的转化率,需要对合成过程中各组分的含量进行快速测定,及时指导最优合成条件的选择.产品扁桃酸中可能含有未反应的苯甲醛和副产品苯甲酸、苯甲醇等杂质.以往采用非水溶剂酸碱滴定分析法测定产品中扁桃酸的含量,但当产品中有苯甲酸等酸性物质存在时,会使测定结果偏高.由于待测样品中组分扁桃酸、苯甲酸酸性使沸点较高,     

A Three‐Site Mechanism for Agonist/Antagonist Selective Binding to Vasopressin Receptors

Molecular‐dynamics simulations with metadynamics enhanced sampling reveal three distinct binding sites for arginine vasopressin (AVP) within its V₂‐receptor (V₂R). Two of these, the vestibule and intermediate sites, block (antagonize) the receptor, and the third is the orthosteric activation (agonist) site. The contacts found for the orthosteric site satisfy all the requirements deduced from mutagenesis experiments. Metadynamics simulations for V₂R and its V_1aR‐analog give an excellent correlation with experimental binding free energies by assuming that the most stable binding site in the simulations corresponds to the experimental binding free energy in each case. The resulting three‐site mechanism separates agonists from antagonists and explains subtype selectivity.     

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。     

An Efficient and Simple Approach to Predict Kovat's Indexes of Polychlorinated Naphthalenes in Gas Chromatography

Molecular structures of polychlorinated naphthalenes were numerically described with a simple but efficient encoding method. Correspondingly a set of structural parameters were obtained for these compounds and linearly correlated with their gas chromatography retention indexes. A quantitative structure‐retention relationship Model (M1) was developed by using multiple linear regression (MLR) with correlation coefficient R = 0.9880 between the numeric structural codes and the gas chromatography retention indexes of 62 polychlorinated naphthalenes. If the “leave‐one‐out” cross‐validation procedure was employed to construct QSPR model for all samples, the second model M2 with the correlation coefficient being R = 0.9839 was generated. The structural codes of polychlorinated naphthalenes were tested with MLR for estimation and prediction of the GC RI by models M1 and M2, and the results obtained were satisfactory.     

静态GM（0,6）灰色模型在预测气相色谱保留指数上的应用

本文从麦克雷诺（ＭｃＲｅｙｎｏｌｄｓ）相常数法出发推导了五种标准物质与任意溶质ｉ的色谱保留指数之间的关系符合灰色ＧＭ（０，６）模型，对它们进行了灰色建模。获得了很高的模型精度，并根据模型式预测了涂有不同固定液色谱柱中的溶质ｉ的保留指数。通过预测值与文献值的比较，得到了良好的预测精度。     

Simultaneous Optimization of Surfactant Concentration and Organic Modifier in Micellar Liquid Chromatography. Application to the Separation of Phenolic Compounds

ABSTRACT

The separation selectivity of eighteen phenolic derivatives in micellar high-performance liquid chromatography was studied as a function of parameters on which it depends: surfactant and organic modifier concentration. The surfactant used in this study was cetyltrimethylammonium bromide, and as organic modifier methanol. An iterative regression optimization strategy for these two parameters has been used. The equation that best explains the experimental

results is 1/k' = A +Bμ + Cφ + DμΦ. We propose the use of this model in conjunction with the appropriate factorial design to predict the solute retention behaviour in micellar liquid chromatography with hibrid eluents.     

胶束电动色谱法测定五维他口服溶液中维生素B_1、B_2、B_6、烟酰胺、泛酸钙与苯甲酸钠

建立了胶束电动色谱(MEKC)法通过波长切换同时测定五维他口服溶液中的维生素B_1、B_2、B_6、烟酰胺、泛酸钙及苯甲酸钠含量的方法,并优化了检测波长、十二烷基硫酸钠(SDS)的浓度、分离电压、缓冲液浓度及pH值等实验条件。最佳分离条件为以未涂渍的标准熔融石英毛细管柱(75μm×50 cm,有效长度42 cm)为分离通道;40 mmol/L硼酸+40 mmol/L硼砂+20 mmol/L SDS(pH 9.0)为运行缓冲液,分离电压20 kV,柱温25℃,检测波长为270 nm(维生素B_1、B_2、B_6、烟酰胺及苯甲酸钠)和200 nm(泛酸钙),电动进样10 kV、进样时间10 s。结果显示,6种化合物可在13 min内实现基线分离,且在一定质量浓度范围内线性良好,相关系数(r)不小于0.998 9;3个加标水平下的平均回收率为97.0%～103%,RSD为0.60%～1.8%。该方法快速、准确,可用于五维他口服溶液中维生素B_1、B_2、B_6、烟酰胺、泛酸钙及苯甲酸钠的含量测定。     

Use of Genetic Algorithms and Artificial Neural Networks to Predict the Resolution of Amino Acids in Thin-Layer Chromatography

JPC – Journal of Planar Chromatography – Modern TLC - A novel method is proposed for optimization of simultaneous thinlayer chromatographic separation of seven amino acids. For this...     

Influence of Organic Modifier Additives to Separate Steroids by Micellar Electrokinetic Chromatography: Determination of Solute-Micelle Association Constants at Different Acetonitrile Concentrations

In this report, the determination of testosterone, progesterone, estrone, 17-β-estradiol, and ethynilestradiol by micellar electrokinetic chromatography (MEKC) is described. Several organic modifiers were investigated using sodium dodecyl sulfate as the surfactant agent in the background electrolyte. The effect of the acetonitrile concentration on the migration time of the steroids and on the selectivity was also studied by using different background electrolytes. Under the optimized conditions that included a sodium tetraborate (pH 9.3; 25 mM) buffer with 10 mM sodium dodecyl sulfate, 20% (v/v) of acetonitrile, 27 kV running voltage, and injection with a plug of background electrolyte (7 mbar × 1 s), the analytical performance of the method was evaluated. Good linearity (correlation coefficients, R ² ≥ 0.99) and adequate precision were achieved, with limits of detection of 1.27, 2.17, 0.6, 1.13, and 1.7 µg/mL for testosterone, progesterone, estrone, 17-β-estradiol, and ethynilestradiol, respectively. To study the effect of the acetonitrile concentration on the solute-micelle interaction, the retention factor and association constants were determined. In all cases, the association constants decreased by increasing the acetonitrile concentration from 10% to 30%, suggesting that the presence of large amounts of organic modifier decreased the steroid-micelle interactions.     

A Portable Fill‐and‐Flow Channel Biosensor with an Electrode to Predict the Effect of Interferences

A portable fill‐and‐flow channel biosensor with a “predictor electrode” is described. The predictor electrode, on the opposite channel wall and upstream of the detector electrode, allows direct evaluation of the current due to interfering species at the detector electrode. A model is developed which shows that the reaction at the upstream predictor electrode has no significant effect on the concentration distribution of the interfering species at the detector electrode. This enables a straightforward correction of the current at the detector electrode and a determination of the analyte concentration. The effect of interference from ascorbic acid in the detection of glucose in samples was efficiently removed by using such a concept. The recovery of glucose from samples containing ascorbic acid was 103% (s=12%, n=3). The approach was also applied to a biosensor for the determination of glucose in red wine samples containing polyphenolic interferents.     

不同纵横比一水草酸钙晶体的合成、表征、吸附性能及其对肾上皮细胞的毒性差异

合成了长宽比分别为1∶2、1∶3、1∶4和1∶5的4种一水草酸钙(COM)晶体COM-1∶2、COM-1∶3、COM-1∶4和COM-1∶5,采用X射线衍射、傅里叶变换红外光谱、扫描电子显微镜(SEM)、ζ电位仪和比表面测试仪等对其理化性质进行了表征。SEM图片显示晶体的宽度相近,但长度分别为(3±0.3)μm、(5.2±0.3)μm、(7.0±0.7)μm和(8.8±1.2)μm。随着反应温度升高,生成的晶体长度变长;搅拌速度越大,生成的晶体尺寸越小;随着添加剂明胶的浓度减小,COM晶体的(101)面被拉长。细胞活力、细胞总死亡率和活性氧检测表明,不同长宽比COM对人肾近端上皮细胞(HK-2)的毒性大小为COM-1∶2>COM-1∶3>COM-1∶4>COM-1∶5>对照组,SEM检测证明4种COM晶体均能够黏附到细胞表面。毒性差异与以下各原因呈正相关：晶体大比例的(101)晶面、大的比表面积、大的细胞-晶体剪切应力。