Eco‐friendly ionic liquid assisted capillary electrophoresis and α‐acid glycoprotein‐assisted liquid chromatography for simultaneous determination of anticancer drugs in human fluids

In the current work, two eco‐friendly analytical methods based on capillary electrophoresis (CE) and reversed phase liquid chromatography (RPLC) were developed for simultaneous determination of the most commonly used anticancer drugs for Hodgkin's disease: methotrexate (MTX), vinblastine, chlorambucil and dacarbazine. A background electrolyte (BGE) of 12.5 mmol/L phosphate buffer at pH 7.4 and 0.1 µmol/L 1‐butyl‐3‐methyl imidazolium bromide (BMImBr) ionic liquid (IL) was used for CE measurements at 250 nm detection wavelength, 20 kV applied voltage and 25 °C. The rinsing protocol was significantly improved to reduce the adsorption of IL on the interior surface of capillary. Moreover, RPLC method was developed on α‐1‐acid glycoprotein (AGP) column. Mobile phase was 10 mmol/L phosphate buffer at pH 6.0 (100% v/v) and flow rate at 0.1 mL/min. As AGP is a chiral column, it was successfully separated l ‐MTX from its enantiomer impurity d ‐MTX. Good linearity of quantitative analysis was achieved with coefficients of determinations (r²) >0.995. The stability of drugs measurements was investigated with adequate recoveries up to 24 h storage time under ambient temperature. The limits of detection were <50 and 90 ng/mL by CE and RPLC, respectively. The using of short‐chain IL as an additive in BGE achieved 600‐fold sensitivity enhancement compared with conventional Capillary Zone Electrophoresis (CZE). Therefore, for the first time, the proposed methods were successfully applied to determine simultaneously the analytes in human plasma and urine samples at clinically relevant concentrations with fast and simple pretreatments. Developed IL‐assisted CE and RPLC methods were also applied to measure MTX levels in patients’ samples over time. Copyright © 2014 John Wiley & Sons, Ltd.     

Anticancer SAR establishment and novel accruing signal transduction model of drug action using biscoumarin scaffold

In this paper, we have established methylenebis (4-hydroxy-2H-chromen-2-one) as a promising anticancer scaffold with kinesin spindle protein (KSP) inhibitory activity under malignant condition. A series of biscoumarin derivatives (MN1 to MN30) with different substituent were synthesized, and their anticancer activity was explored. Six biscoumarin derivatives that were found active were further selected to formulate organic nanoparticles (ONPs). Anticancer activity of both the forms (viz conventional and ONPs) was compared. MN30 was found most potent whereby MN10 showed good anticancer activity in both, i.e., conventional and ONP form; the structural activity relationship (SAR) study has been established. Computational investigation revealed biscoumarin scaffold as a suitable pharmacophore to bind against KSP protein. Molecular dynamics simulation studies revealed protein-ligand stability and dynamic behavior of biscoumarin-KSP complex. Finally, accruing signal transduction model was formulated to explain the observed MTT trend of conventional and ONP form. The model seems useful towards solving population specific varied results of chemotherapeutic agents. According to the model, MN10 and MN30 derivatives have good pharmacodynamics inertia and therefore, both the molecules were able to provide dose-dependent cytotoxic results.     

Spray Freeze-drying – The Process of Choice for Low Water Soluble Drugs?

Most of the novel highly potent drugs, developed on the basis of modern molecular medicine, taking into account cell surface recognition techniques, show poor water solubility. A chemical modification of the drug substance enhancing the solubility often decreases the pharmacological activity. Thus, as an alternative an increase of the solubility can be obtained by the reduction of the size of the drug particles. Unfortunately, it is often difficult to obtain micro or nanosized drug particles by classical or more advanced crystallization using supercritical gases or by milling techniques. In addition, nanosized particles are often not physically stable and need to be stabilized in an appropriate matrix. Thus, it may be of interest to manufacture directly nanosized drug particles stabilized in an inert hydrophilic matrix, i.e. nanostructured and nanocomposite systems. Solid solutions and solid dispersions represent nanostructured and nanocomposite systems. In this context, the use of the vacuum-fluidized-bed technique for the spray-drying of a low water soluble drug cosolubilized with a hydrophilic excipient in a polar organic solvent is discussed. In order to avoid the use of organic solvents, a special spray-freeze-drying technique working at atmospheric pressure is presented. This process is very suitable for temperature and otherwise sensitive drugs such as pharmaproteins.     

Thermal decomposition of a generation 4.5 PAMAM dendrimer platinum drug conjugate

A nanoscale multivalent platinum drug based on a poly(amidoamine) [PAMAM] dendrimer (generation 4.5, carboxylate surface) has been synthesized and fully characterized using a variety of spectroscopic, chromatographic and thermal methods. Treatment of the dendrimer with an aqueous solution containing an excess diaquo(cis-1,2-diaminocyclohexane)platinum(II) produces a conjugate containing approximately forty (diaminocyclohexane)platinum(II) moieties at the surface of the dendrimer. This material undergoes smooth two-stage thermal decomposition to provide residual platinum oxide reflecting the platinum loading in the drug.     

用激光散斑场检测药液内杂质含量分布

本文分析了利用散斑斑纹检测大输液药品杂质含量的机理，报道了检测大输液药品杂质的实例．     

In vitro screening of the action of non-steroidal anti-inflammatory drugs on hypochlorous acid-induced hyaluronan degradation

The antioxidative effect of two non-steroidal anti-inflammatory drugs was studied in vitro by measuring the kinetics of degradation of high-molecular weight hyaluronan (HA) in a system comprising hypochlorous acid + CuCl₂ + ascorbic acid using a Brookfield rotational viscometer equipped with a Teflon cup and spindle of coaxial cylindrical geometry. The changes in HA chemical structure were investigated by chemiluminometry. When sodium naproxen was added to the system during a running degradative process its inhibitory effect was clearly shown. The inhibition was dependent on the drug concentration. However, when this drug was added to the system before the initiation of HA degradation, no inhibition was seen even at the highest drug concentration tested. The inhibitory effect of acetylsalicylic acid was achieved with a relatively low concentration of the drug and was independent of the experimental model used.     

Thermoanalytical methods in pharmaceutical technology

A short survey is given of some aspects of the application of thermoanalytical methods, especially differential thermal analysis (DTA), differential scanning calorimetry (DSC) and thermogravimetry (TG), in solid-dosage technology. The usefulness of these methods in the prediction of drug-excipient compatibility, studies of solid-dispersion systems, the analysis of enantiomers and racemates, measurement of the time of tablet disintegration, the analysis of drug formulations and studies of the processes of grinding and drying of drugs is discussed.

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Zusammenfassung Es wird ein kurzer Überblick über einige Aspekte der Anwendung von thermoanalytischen Methoden, insbesondere von DTA, DSC und TG in der Feststoffdosierung gegeben. Weiterhin wird die Nützlichkeit dieser Methoden bei der Voraussage der Bindemittelverträglichkeit, bei der Untersuchung disperser Feststoffsysteme, bei der Analyse von Enantiomeren und Racematen, bei der Messung der Tablettenzerfallszeit, bei der Analyse der Arzneimittelformierung und bei der Untersuchung von Mahl- und Trocknungsprozessen bei Arzneimitteln diskutiert.

     

表面等离子体子共振技术用于分析手性药物与蛋白作用差异的研究

利用自行设计组装的一套以白色发光二极管为光源的新型表面等离子体子共振传感器实验装置测量了手性药物D-苯甘氨酸与L-苯甘氨酸与人血清白蛋白和鼠血清白蛋白的结合程度, 可以看到这一对手性药物与血清蛋白的结合程度的差异, 通过这种方法可以区分一对手性药物中的不同异构体. 与现在的手性分析方法比较, 这种方法具有不用标记、样品用量少、仪器易于自动化及小型化等优点.     

长光路光度法测定中药材中痕量硒

本文研究了用长光路光度法测定痕量硒。在酸性溶液中，Ｓｅ（Ⅳ）催化ＫＣｌＯ３氧化苯肼成偶氮离子，继而与变色酸生成红色偶氮化合物。硒含量在１．０×１０－９～２．０×１０－７ｇ／ｍＬ范围内遵守比尔定律。巯基棉分离后，测定中药材中总硒，获得满意结果。