LC determination of atropine sulfate and scopolamine hydrobromide in pharmaceuticals

An accurate, simple, reproducible and sensitive method for the determination of atropine sulfate and scopolamine hydrobromide has been developed and validated. Atropine sulfate and scopolamine hydrobromide were separated using a microBondapack C(18) column by isocratic elution with flow rate 1.0 ml/min. The mobile phase composition was methanol, water, formic acid (165:35:1; v/v/v) and pH adjusted 8.3 with triethylamine. The samples were detected at 230 nm using photo-diode array detector. The linear range of detection for atropine sulfate (I) and scopolamine hydrobromide (II) were between 10.38 and 1038 microg/ml with a limit of quantification (LOQ) of 10.38, 10.00 and 1034 microg/ml with an LOQ of 10.00 microg/ml respectively. The linearity, range, peak purity, selectivity, system performance parameters, precision, accuracy, robustness and ruggedness for (I) and (II) were also shown acceptable values.     

Gastro-intestinal sustained release of phytic acid by molecularly imprinted microparticles

In this work, the possibility to employ molecularly imprinted polymers as base excipients for controlled drug delivery devices was demonstrated. As template molecule, our attention was focused on phytic acid, a water soluble antioxidant compound. The possibility to raise a controlled/sustained release of an antioxidant agent is very useful from an application point of view; in recent years, indeed, biomedical applications of antioxidants have greatly grown because the link between human diseases and oxidative stress were proved. Polymers were synthesized using methacrylic acid as functional monomer and N,N′-Ethylenebis(acrylamide) as crosslinker. After the evaluation of the imprinting efficiency of the synthesized materials by binding experiments in which the percentage of phytic acid bounded by the molecularly imprinted polymers was found to be remarkably higher compared to the non-imprinted ones, MIP were tested as a controlled release device for the antioxidant in gastrointestinal simulating fluids.     

Rapid determination of theophylline in serum by selective extraction using a heated molecularly imprinted polymer micro-column with differential pulsed elution

Molecular imprinting of theophylline in poly(methacrylic acid ethylene dimethacrylate) form binding sites with complementary size, shape and chemical functionalities to theophylline. This molecularly imprinted polymer (MIP) can be packed into a micro-column for selective solid phase extraction (SPE) of theophylline from 20 microl of sample solution. Its chemical inertness and thermal stability allow the use of various organic solvents and elevated column temperatures for effective binding of theophylline. Non-specific adsorption of interfering drugs on the MIP surface is eliminated by an intermediate wash with 20 microl of acetonitrile, prior to quantitative desorption of the bound theophylline by 20 microl of methanol for in-line UV spectrophotometric determination. In this differential pulsed elution (DPE) technique, both the column temperature and solvent flow rate can be optimized to enhance selectivity. Application of this micro-analytical method, molecularly imprinted solid phase extraction DPE (MISPE-DPE), is demonstrated for accurate determination of theophylline in human blood serum. The method is validated over a linear range from 2 microg/ml to at least 20 microg/ml.     

HPLC法测定华山参滴丸中东莨菪碱、阿托品及东莨菪内酯的含量

目的:建立HPLC法测定华山参滴丸中东莨菪碱、阿托品及东莨菪内酯的含量。方法:采用资生堂CAPCELL-PAK C18(4.6 mm×250 mm,5μm)色谱柱,以乙腈-甲醇-磷酸氢二钠缓冲液(15∶4∶81)为流动相,流速1.0 mL·min-1,东莨菪碱、阿托品检测波长210 nm(0～15 min),东莨菪内酯检测波长为344 nm(15.1～30 min),柱温30℃。结果:东莨菪碱、阿托品及东莨菪内酯的线性范围分别为0.04～3.95,0.04～4.10,0.05～0.54μg(r=0.9999);平均回收率(n=6)分别为97.58%(RSD=1.3%),98.65%(RSD=1.3%),98.42%(RSD=1.8%)。结论:本文方法简便、准确,可以用于华山参滴丸中东莨菪碱、阿托品及东莨菪内酯的含量测定。     

Uniformly sized molecularly imprinted polymers for bisphenol A and beta-estradiol: retention and molecular recognition properties in hydro-organic mobile phases

Uniformly sized molecularly imprinted polymers (MIPs) for bisphenol A (BPA) have been prepared using ethylene glycol dimethacrylate (EDMA) as a cross-linker and methacrylic acid, 2-diethylaminoethyl methacrylate or 4-vinylpyridine (4-VPY) as a functional monomer or without use of a functional monomer. The MIPs obtained for BPA were evaluated using a mixture of phosphate buffer (or water) and acetonitrile or only acetonitrile as the mobile phase. Among the MIPs prepared, that using 4-VPY showed the highest retentivity and selectivity for BPA. The highest selectivity factor, which is defined as the ratio of the retention factors (k) on the molecularly imprinted and non-imprinted polymers, k_imprinted/k_{non-imprinted}, was 9.4 for BPA on the BPA-imprinted 4-VPY–co-EDMA polymers, while that for β-estradiol on the β-estradiol-imprinted 4-VPY–co-EDMA polymers was 2.4. The differences in the selectivity factors between BPA and β-estradiol on the respective MIPs could be ascribable to differences in the number of interaction sites. It is plausible that the phenol groups of BPA could interact with two pyridyl groups of the MIP by hydrogen bonding interactions, while there is only one such site for β-estradiol. Furthermore, the results suggest that hydrophobic and hydrogen bonding interactions can play an important role in the retention and recognition of BPA and β-estradiol in the hydro-organic mobile phase, while hydrogen bonding interactions seem to be useful for the retention and recognition when acetonitrile is used as the mobile phase.     

Molecularly imprinted polymers for alpha-tocopherol delivery

Biomedical applications of antioxidants have increased dramatically since the link between human diseases and oxidative stress was established. This paper focuses on alpha -tocopherol and on the possibility of employing molecularly imprinted polymers as a controlled release device for alpha-tocopherol in gastrointestinal simulating fluids. Polymers were synthesized using methacrylic acid as functional monomer and ethylene glycol dimethacrylate as cross-linker. Considerable differences in recognition characteristics between imprinted and non-imprinted polymers, both in organic and in aqueous media, were observed. Imprinted polymers bound much more alpha-tocopherol and showed a controlled/sustained drug release capacity in gastrointestinal simulating fluids.     

三唑醇分子印迹聚合物的制备及在食品检测中的应用

目的:制备三唑醇分子印迹聚合物(MIP),建立食品中三唑醇残留检测方法。方法:以三唑醇为模板分子,α-甲基丙烯酸(MAA)为功能单体,乙二醇二甲基丙烯酸酯(EDMA)为交联剂,采用本体聚合法合成了MIP,以该MIP为固相萃取剂处理样品,并采用高效液相色谱法检测,使用Shim VP-C18色谱柱(150 mm×4.6 mm,5μm),以甲醇-水(体积比为40∶60)作为流动相,检测波长为224 nm。结果:三唑醇线性范围为0.1～200μg.mL-1,线性相关系数为0.9998,检出限为0.5μg.g-1,在2μg.g-1和10μg.g-1添加水平下,平均回收率在79.3%～86.0%之间,RSD≤2.3%(n=5)。结论:该方法灵敏度较高,重现性好,检测快速,是检测食品中三唑醇杀菌剂残留的有效方法。     

Development of 2-(dimethylamino)ethyl methacrylate-based molecular recognition devices for controlled drug delivery using supercritical fluid technology

This work reports the development of a novel potential body-friendly oral drug delivery system, which consists of a biocompatible molecularly imprinted polymer (MIP), with pH sensitive character and low cross-linking degree (20.2 wt%), synthesized and processed in supercritical carbon dioxide. The MIP is synthesized using 2-(dimethylamino)ethyl methacrylate (DMAEMA) as functional monomer and ethylene glycol dimethacrylate (EGDMA) as cross-linker, and ibuprofen as molecular recognition template. The imprinted matrix was able to show a higher affinity towards ibuprofen than its corresponding non-imprinted polymer (NIP) meaning that the molecular imprinting in scCO₂ was efficient even using a low crosslinking degree. MIP showed a significant molecular recognition towards the template, presenting higher drug uptake ability in the supercritical impregnation step, loading 33.1 wt% of ibuprofen compared to only 10.2 wt% for the NIP polymer. In vitro drug release experiments, simulating an oral administration, showed different release profiles at pH 2.2 and pH 7.4. Zeta potential measurements were performed to both MIP and NIP showing that the imprinting process has a significant influence on the charge of the polymeric particles. Cytotoxicity assays performed with human colorectal carcinoma-derived Caco-2 cells demonstrated that the polymers are biocompatible and could be potentially used in drug delivery applications.     

分子印迹液相色谱整体柱制备及最新应用

分子印迹整体柱是结合分子印迹聚合物(MIP)和整体柱而形成的,具有选择性高、成本低、理化性质稳定、传质快速和通透性高等多种优点,近年来被认为是制备高性能色谱固定相材料最有前途的方法之一,尤其是制备MIP液相色谱整体柱.本文重点论述了印迹整体柱材料作为液相色谱固定相的各种制备方法及在药物分离检测中的最新研究应用.另外也表述了一些关于印迹整体柱未来发展趋势的观点.     

分子印迹固相萃取-高效液相色谱法分析2种三唑类杀菌剂残留

目的:建立了分子印迹固相萃取-高效液相色谱法检测食品中2种三唑类杀菌剂残留的方法。方法:分别以三唑醇、烯唑醇为模板分子,α-甲基丙烯酸为功能单体,乙二醇二甲基丙烯酸酯为交联剂,采用本体聚合法合成分子印迹聚合物。将制得的三唑醇、烯唑醇聚合物按质量比1:1混合,制成固相萃取柱用于样品的前处理,并采用高效液相色谱法检测。结果:在低和高浓度添加水平下,平均回收率在78.7%～94.3%之间,RSD在1.8%～2.4%之间(n=5)。结论:该方法灵敏度高,精密度好,适合于同时检测食品中三唑醇和烯唑醇2种三唑类杀菌剂残留。     

新诺明分子印迹传感器的制备及应用研究

目的以吡咯为单体在玻碳电极表面电聚合一种新诺明分子印迹膜。方法研究了聚吡咯、新诺明浓度、扫描圈数及扫描速率对印迹膜制备的影响,并探讨检测液的pH值、乙腈与水的体积比对响应电流的影响。采用循环伏安法及电化学交流阻抗技术对分子印迹膜进行表征。结果在最佳实验条件下新诺明的浓度在2．50×10^-5～7．50×10^-4mol·L^-1及7．50×10^-4～2．00×10^-3mol·L^-1内时,差分脉冲伏安法的峰电流响应值呈现线性关系（线性相关系数分别为0．9958和0．99671,检出限（S／N=3）为2．80×10^-6mol·L^-1。结论印迹电极也显示出较好的选择性、重复性、稳定性。将此印迹传感器对复方新诺明药品中磺胺甲嗯唑的含量进行了测定,回收率在94．2％～105．0％。     

Investigation of the effect of space environment on the contents of atropine and scopolamine in Datura metel by capillary zone electrophoresis

The seeds of Datura metel were carried aboard a retrievable satellite and exposed to space environment. The effects of space environment (weightlessness and ionizing radiation) on the contents of atropine and scopolamine in D. metel were investigated by using an effective capillary zone electrophoresis (CZE) method, which employed 50 mmol/l phosphate buffer (pH 8) containing 10% (v/v) tetrahydrofuran as the running buffer. The results showed that the contents of atropine and scopolamine varied to some extent, and the earth-control group has the lowest content of atropine. However, the variation of atropine and scopolamine contents in three groups was not obvious based on t-test. At the same time, the optimization of the separation was discussed in detail and the two compounds were completely separated within 10 min with satisfactory repeatability and calibration linearity.     

槲皮素-铝配位分子印迹聚合物的制备及其结合特性研究*

目的 制备槲皮素-Al（Ⅲ）配位分子印迹聚合物,并且对其特性进行研究,为分子印迹技术和生物识别过程及机理的进一步理解奠定基础。方法 以α-甲基丙烯酸为功能单体、槲皮素- Al（Ⅲ）配合物为模板分子在甲醇中合成金属配位键的印迹聚合物,并且通过紫外光谱、红外光谱、透视电镜分析及吸附试验对聚合物进行了表征及性能的研究。结果 紫外光谱表明,槲皮素、Al（Ⅲ）与α-甲基丙烯酸发生了三元配位作用,槲皮素- Al（Ⅲ）模板印迹聚合物对槲皮素- Al（Ⅲ）的配合物表现出明显的吸附选择性和特异性。结论 本文以α-甲基丙烯酸为功能单体、槲皮素- Al（Ⅲ）配合物为模板分子在甲醇中成功合成了金属配位键的印迹聚合物,制备的槲皮素- Al（Ⅲ）金属配位印迹聚合物对槲皮素-Al（Ⅲ）配合物具有特异的识别作用,在分离、检测样品中的槲皮素方面具有较好的应用前景。     

Variation of scopolamine and atropine in different parts of Datura metel during development

Scopolamine and atropine contents in the whole plant of Datura metel L. increased gradually with the progress of developmental growth, and were most pronounced when the plant was at the end of its reproductive stage. The highest percentage of scopolamine accumulation in the root was after 16 weeks. The root was the organ which often accumulated higher amounts of atropine. The aerial parts, if compared with the root of the plant, usually accumulated relatively higher amounts of scopolamine and relatively lower amounts of atropine.     

阿托品流通传感器的研制及其在流动注射分析中的应用

本文报道了一种新型的传感器——阿托品流通传感器及其在流动注射分析中的应用。采用流动注射分析法测定了硫酸阿托品片剂和注射剂、盐酸山莨菪碱注射剂、氢溴酸东莨菪碱注射剂及颠茄酊、颠茄片和复方颠茄片的含量,并对硫酸阿托品片和颠茄片含量均匀度进行了测试,方法简便、快速,样品分析速度可达每小时60～100次。     

Molecularly imprinted solid phase extraction-pulsed elution-mass spectrometry for determination of cephalexin and alpha-aminocephalosporin antibiotics in human serum

A highly selective molecularly imprinted solid phase extraction (MISPE)-pulsed elution (PE) method coupled with electrospray mass spectrometry (MS) was developed for the rapid screening and determination of cephalexin in alpha-aminocephalosporin antibiotics. This method involved the solid phase extraction of cephalexin using a molecularly imprinted polymer micro-column, and pulsed elution with 1% trifluoroacetic acid in methanol, which contains sulindac as an internal standard for enhanced precision in MS detection. An LC/MS spectrometer was operated in the positive electrospray mode, and the selected-ion-recording (SIR) function was employed to detect the molecular ions of cephalexin, cefradine, cefadroxil and sulindac at m/z 348, 350, 363 and 357. Linearity was achieved in the cephalexin concentration range from 0.3 to 25microg/ml (or 5-500ng) (R(2) = 0.998). The detection limit was estimated at 0.04microg/ml (or 0.8ng) of cephalexin. Advantages of the newly developed MISPE-PE-MS, over the previously reported MISPE-DPE-FPE-UV, were evidenced in terms of detection limit, analysis time, solvent consumption, and simplicity of method development.     

Syntheses of deuterium labelled atropine and scopolamine

Easy preparative scale syntheses of deuterium labelled atropine and scopolamine are described. [²H₃]‐atropine and [²H₃]‐scopolamine are obtained in good yield and good isotopic purity in two steps starting from the unlabelled alkaloids. Copyright © 2009 John Wiley & Sons, Ltd.     

Determination of atropine in pharmaceutical dosage forms containing vegetal preparations, by high-performance liquid chromatography with U.V. and electrochemical detection

A method to test the uniformity of Belladonna powder in multicomponent pharmaceutical dosage forms, by the determination of atropine, is described. The procedure involves a liquid-liquid extraction, followed by liquid chromatographic separation of atropine, apoatropine and scopolamine and quantification of atropine with either ultraviolet or electrochemical detection. The method is shown to be selective, sensitive and offers good reproducibility. A detailed study of the electrochemical properties of atropine also is undertaken.     

抗胆碱能药物分子印迹聚合物的液相色谱行为

目的:以三种抗胆碱能药物为模板,合成分子印迹聚合物(molecularly imprinted polymer,MIP),考察不同流动相系统中MIP对于待测物的色谱分离行为及识别机理。方法:以盐酸新托品、盐酸苯环壬酯和盐酸戊乙奎醚为模板分子,甲基丙烯酸为功能单体,三羟甲基丙烷三甲基丙烯酸酯为交联剂,在乙腈中合成MIP,研磨后填装液相色谱柱,分别在有机溶剂流动相(乙酸-乙腈)和极性介质流动相(乙酸铵-乙腈)中考察MIP对盐酸新托品、盐酸苯环壬酯和盐酸戊乙奎醚的色谱分离行为。结果:在有机溶剂流动相中,各MIP对待测物均表现出强吸附;在极性介质流动相中,三种抗胆碱能药物的保留时间为t盐酸苯环壬酯相似文献