Monoliths with chiral surface functionalization for enantioselective capillary electrochromatography

The state-of-the-art in CEC enantiomer separations with monolithic capillary columns is comprehensively reviewed. The various types of monolithic columns comprising in situ organic polymer monoliths, molecularly imprinted polymer (MIP) monoliths, silica monoliths and monoliths made from particles are discussed with a focus on materials’ synthesis, chemistry and properties as well as column aspects. Monolithic MIP-type porous layer open-tubular (PLOT) columns are treated herein as well. From this survey of the literature, the authors come to the conclusion that monolithic silica capillaries appear to become the preferred column type for CEC enantiomer separations of low-molecular drugs and other chiral pharmaceuticals or chemicals.     

槲皮素分子印迹聚合物的合成及表征

目的利用分子印迹技术制备槲皮素分子印迹聚合物(MIPs)。方法以槲皮素为模板分子,丙烯酰胺为功能单体,乙二醇二甲基丙烯酸酯为交联剂,偶氮二异丁腈为引发剂,分别在无水乙醇和四氢呋喃为致孔剂的作用下,采用沉淀聚合法、本体聚合法制备槲皮素MIPs;利用紫外光谱、红外光谱选择模板分子与功能单体间的最佳配比;通过扫描电镜(SEM)考察了MIPs的微观结构。采用平衡和等温吸附实验对2种方法制备的MIPs的吸附平衡时间和最大吸附量进行考察,并对特异性吸附能力进行研究。结果沉淀聚合法制备的槲皮素MIPs具有均匀规则的球状结构,在吸附动力学和等温吸附实验中发现有较快的吸附速度和较大的吸附量,在芦丁和槲皮素的选择性吸附过程中聚合物对槲皮素具有较高的特异性识别能力。结论沉淀聚合法制备的MIPs以吸附量大、选择性强,为中药黄酮类复杂化学成分的分离、富集提供一种新的研究方法,同时也为其他中药化学成分的研究提供借鉴。     

Determination of haloperidol in biological samples using molecular imprinted polymer nanoparticles followed by HPLC-DAD detection

In this study an extraction procedure using molecular imprinted polymer nanoparticles for the determination of haloperidol in biological samples is proposed. The haloperidol imprinted polymer nanoparticles were synthesized successfully by precipitation polymerization in a flask containing haloperidol as a template, ethyleneglycoldimethacrylate as a crosslinking agent, methacrylic acid as a functional monomer, and 2,2′-azobisisobutyronitrile as an initiator. The leached and unleached polymer nanoparticles have been characterized by infrared spectroscopy and scanning electron microscopy. The effect of different variables such as the pH of solution, uptake and elution time, type, and the least amount of eluent for elution of haloperidol from polymer was evaluated. Extraction efficiencies more than 97% were obtained by elution of the polymer with 1.5 mL of methanol–acetic acid–trifluoroacetic acid 79.9:20:0.1. Under optimal conditions maximum adsorption capacity was obtained 153.84 mg g⁻¹. The detection limit of the proposed procedure was between 0.2 and 0.35 μg L⁻¹. Finally this method was applied to the determination of haloperidol in plasma and urine samples and satisfactory results were achieved (RSD < 6.9%).     

灯盏花素聚丙烯酸酯纳米球的制备及载药机理探讨

目的:制备灯盏花素聚丙烯酸酯纳米球,研究聚丙烯酸酯纳米球与灯盏花素之间的载药机理。方法:采用微乳液聚合法制备聚丙烯酸酯纳米球,表面活性剂为十二烷基硫酸钠(SDS),助表面活性剂为丁醇,单体为甲基丙烯酸(MAA)、甲基丙烯酸丁酯(BMA),交联剂为三羟甲基丙烷三甲基丙烯酸酯(TRIM),引发剂为偶氮二异丁乙腈(AIBN);灯盏花素的载药分别采用在聚合反应之前和之后加入二种方式。结果:制备的聚丙烯酸酯纳米球大小在50nm左右,表面电势ζ为-27.2mv,负载灯盏花素以后纳米球电位增大。灯盏花素包封到聚丙烯酸酯纳米球上时,其载药量与加入药量呈线性相关;灯盏花素负载到聚丙烯酸酯纳米球上时,载药量呈层状增加。结论:通过微乳液聚合制备的聚丙烯酸酯纳米球可用于包封脂溶性中药成分。     

GC-MS测定富马酸卢帕他定中痕量杂质偶氮二异丁腈

目的 采用气相色谱-质谱联用法测定富马酸卢帕他定中偶氮二异丁腈（azodiisobutyronitrile,AIBN）杂质的含量。方法 采用DB-624毛细管柱（30 m×0.25 mm,1.4 μm）,程序升温,初始温度为70℃,以12℃·min^-1升到250℃,以氦气为载气,流速为0.6 mL·min^-1,采用电子轰击电离源（EI）,在单离子检测模式（SIM）下选择m/z 69、m/z 54和m/z 41进行检测。结果 AIBN浓度在0.155 2~3.103 μg·mL^-1内与峰面积线性关系良好（r²=0.999 8）;检测限为0.045 μg·mL^-1,定量限为0.15 μg·mL^-1,样品中杂质AIBN测定结果的重复性良好,RSD（n=6）为0.31%;杂质AIBN低、中、高浓度的加样回收率（n=3）分别为103.9%,101.0%,99.4%,RSD（n=3）分别为0.03%,0.11%和0.08%。经检测,3批富马酸卢帕他定供试品中AIBN均未检出。结论 本方法操作简便,结果准确,灵敏度高,可用于富马酸卢帕他定中AIBN的检测。     

HPMA copolymer-cyclic RGD conjugates for tumor targeting

This review describes the design and development of N-(2-hydroxypropyl)-methacrylamide (HPMA) copolymer-cyclic RGD conjugates for targeting tumor angiogenesis. Relative to non-targetable systems, HPMA copolymer-RGD4C and -RGDfK conjugates have shown increased tumor accumulation in a variety of solid tumors including prostate, lung, and breast tumor xenografts. Compared to free peptides, copolymers had increased tumor accumulation and decreased uptake in non-target organs such as the liver and spleen. Clinically relevant imaging agents such as ^99mTc, ¹¹¹In, and Gd enabled in vivo imaging of the constructs by scintigraphy and magnetic resonance techniques. Targeted delivery of ⁹⁰Y, a radiotherapeutic agent by HPMA copolymer-RGD4C conjugates resulted in tumor size reduction in mice bearing prostate tumor xenografts. Delivery of the geldanamycin derivative 17-(6-aminohexylamino)-17-demethoxygeldanamycin by HPMA copolymer-RGDfK conjugates resulted in increased tumor concentration of the free drug in a prostate xenograft model. These constructs show promise for targeted delivery of therapeutics and imaging agents to solid tumors.     

2,2'-Azobis(isobutyronitrile)-derived alkylperoxyl radical scavenging activity assay of hydrophilic antioxidants by employing EPR spin trap method

As interest in the study of antioxidant intake from foods and other agricultural products increases, methods for performing radical scavenging activity assays based on the electron paramagnetic resonance spectroscopic method, in which there is no interference from the sample color and turbidity, are required. In this study, we have developed a rapid and simple electron paramagnetic resonance based assay to evaluate the alkylperoxyl radical scavenging activity of several antioxidants. The alkylperoxyl radical species was generated by the photolysis of azo-radical initiator 2,2''-azobis(isobutyronitrile), in which the radical generation rate and period were controlled by the illumination light. The relative alkylperoxyl radical scavenging activity was obtained by a simple formula of competing reaction of antioxidant and spin trap toward the oxygen radical. The scavenging activities toward alkylperoxyl radical and alkoxy radical species were evaluated in six antioxidants. Although quercetin showed the highest activity toward both radicals, the order of the relative activities in the other antioxidants was different mutually between the alkylperoxyl radical and the alkoxyl radical. This alkylperoxyl radical scavenging activity assay based on electron paramagnetic resonance spectroscopy is useful for evaluation of colored and turbid food samples.     

Characterization of a Stable 2,2′-Azobis(2-Methylpropanenitrile) Degradant and Its Use to Monitor the Oxidative Environment During Forced Degradation Studies by Liquid Chromatography/Mass Spectrometry

Azo compounds are commonly used to study radical-mediated degradation of pharmaceutical compounds. The favorable chemical and physical properties of 2,2′-azobis(2-methylpropanenitrile) (AIBN) have made it one of the most widely used compound for these type of studies. This article describes the characterization of a stable product, N-(1-cyano-1-methylethyl)-2-methylpropanamide, formed during the decomposition of AIBN. This product is easily detected by liquid chromatography/mass spectrometry and can serve as a marker to confirm the AIBN is working as intended and to monitor the kinetic formation of free radical species.     

Programming the composition of polymer blend particles for controlled immunity towards individual protein antigens

In order for a more precise control over the quality and quantity of immune responses stimulated by synthetic particle-based vaccines, it is critical to control the colloidal stability of particles and the release of protein antigens in both extracellular space and intracellular compartments. Different proteins exhibit different sizes, charges and solubilities. This study focused on modulating the release and colloidal stability of proteins with varied isoelectric points. A polymer particle delivery platform made from the blend of three polymers, poly(lactic-co-glycolic acid) (PLGA) and two random pH-sensitive copolymers, were developed. Our study demonstrated its programmability with respective to individual proteins. We showed the colloidal stability of particles at neutral environment and the release of each individual protein at different pH environments were dependent on the ratio of two charge polymers. Subsequently, two antigenic proteins, ovalbumin (OVA) and Type 2 Herpes Simplex Virus (HSV-2) glycoprotein D (gD) protein, were incorporated into particles with systematically varied compositions. We demonstrated that the level of in vitro CD8⁺ T cell and in vivo immune responses were dependent on the ratio of two charged polymers, which correlated well with the release of proteins. This study provided a promising design framework of pH-responsive synthetic vaccines for protein antigens of interest.     

Rapid separation and determination of structurally related anthraquinones in Rhubarb by pressurized capillary electrochromatography

A pressurized capillary electrochromatography (pCEC) with monolithic column has been developed for the rapid separation and determination of five structurally related anthraquinones in Rhubarb. The possibility of rapid separation resulted from the unique pore structure with high permeability and favorable mass transfer characteristics of the monolithic stationary phase. The effect factors such as organic modifier, acidity and concentration of running buffer, separation voltage were investigated to acquire the optimum condition. In the 220 nm wavelengths, the five anthraquinones could be baseline-separated rapidly within 5 min with the separation voltage of -20 kV in 10 mmol/L phosphate buffer (pH 6.2) containing 65% acetonitrile. The calibration graphs of rhein, aloe-emodin, emodin chrysophanol and physcion were linear by plotting the peak area against the analytes concentration over the range of 0.2-65, 0.1-30, 0.1-55, 0.5-30 and 0.5-55 microg/mL, respectively. The detection limits of five anthraquinones were ranged from 0.06 to 0.2 microg/mL and the recoveries of Rhubarb samples were about 81.3-86.4% (R.S.D.< or = 5.2%). This proposed method was successfully applied to determination of the five analytes in Rhubarb with satisfactory results.