Preparation of dummy template‐imprinted polymers for the rapid extraction of nonsteroidal anti‐inflammatory drugs residues in aquatic environmental samples

A molecularly imprinted polymer was synthesized and applied as a sorbent in the solid‐phase extraction device. The imprinted polymer was characterized by fourier‐transform infrared spectroscopy and scanning electron microscope. The results revealed that imprinted polymer possess sensitive selectivity and reliable adsorption properties for five NSAIDs. The imprinted polymer was successfully applied to the pre‐concentration for five NSAIDs in different water samples prior to UPLC‐MS/MS. In the early studies, several factors were investigated, including pH adjustment, the kind of elution solvent and the volume of elution solvent. Finally, we found that the pH 5 and an aliquot of 2 mL methanol were suitable for the water samples. The limits of detection and limits of quantitation of five nonsteroidal anti‐inflammatory drugs varied from 0.007 to 0.480 μg L⁻¹ and 0.03 to 1.58 μg L⁻¹, respectively. The spiking recoveries of the target analytes were 50.33‐127.64% at the levels of 0.2 μg L⁻¹, 2 μg L⁻¹ and 5 μg L⁻¹. The precision and accuracy of this method showed a great increase compared with traditional solid‐phase extraction. The developed method was successfully applied to extraction and analysis of NSAIDs in different water samples with satisfactory results which could help us better understand their environmental fate and risk to ecological health.     

Simple and rapid HPLC method for simultaneous determination of multiple antiepileptic drugs in human serum

Summary A very rapid, sensitive and reproducible HPLC method was developed for simultaneous determination of eight anti-epileptic drugs (AEDs): lamotrigine, primidone, ethosuximide, sulthiame, felbamate, phenobarbital, carbamazepine, phenytoin and oxcarbazepine-metabolite (10-hydroxy-carbazepine) in human serum. Sample purification requires only protein precipitation with an appropriate reagent. Separation was by reversed-phase HPLC, using a C18 column, 20% acetonitrile and 40 mM phosphoric acid buffer as mobile phase. Column temperature was set at 50°C, and measurement was by UV detection at 205 nm. The inter and intra-assay coefficients of variation (CV) ranged 1.13–7.10% and 1.14–8.49%, respectively. The absolute (measured) and relative (analytic) recoveries of the drugs ranged 96.7%–104.4% and 97.3%–106.1%, respectively. No interference with other common antiepileptic drugs and analgesics were observed. The method requires only 100 μl serum or less. It is very fast (sample preparation and analysis time approx. 23 min for all 9 AEDs), and suitable for routine clinical use, especially for epileptic patients on polytherapy.     

Capillary zone electrophoresis of basic drugs in non-aqueous acetonitrile with buffers based on a conventional pH scale

Summary The pK _a ^* values of 10 nitrogen-containing basic drugs in non-aqueous acetonitrile were determined from the pH^* dependence of their electrophoretic mobilities. The pH^* scale in the organic solvent was established using background electrolytes with known conventional pK _a ^* values, making further calibration with reference pH electrodes unnecessary. In acetonitrile the pK _a ^* values of analytes (or their conjugated cation acids, BH⁺, respectively) were 5.2±8.9 pK units>those in water. The observed change in pK _a ^* values of cationic analytes was, however, much less than the known respective change for neutral acids type HA. From the pK _a ^* values and the actual mobilities, it is possible to predict pH^* conditions to enable separation of analytes, and this was demonstrated for two pairs of common drugs.     

三种蒙药中微量元素含量与疗效相关性分析

用原子吸收分光光度计测定了蒙药扎木萨－4,阿拉坦－5,阿那日－5中多种微量元素及常量元素的含量。结果表明,这三种健胃消食蒙药中Mg、Fe、Mn、Zn均较高,呈一定相关性,而有害元素Pb、Cd很少,探讨了三种蒙药中微量元素与其疗效的关系。     

高效液相色谱法直接拆分非甾体解热镇痛药物对映体

使用Kromasil CHI-TBB手性固定相,分离了非甾体解热镇痛药卡洛芬,氟吡洛芬,非诺洛芬,酮洛芬,吡咯芬和萘普生等对映体。结果表明,这种以酒石酸二酰胺为手性中心的商业化手性固定相,适合于在正相条件下分离上述药物对映体,对映体分离因子和分析时间可以通过向流动相中添加极性物质如异丙醇,甲基叔丁醚等来进行调节。     

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.

     

考虑合同保质期的快速失效药品的二级供应链库存策略研究

医院药品对保质期和服务水平有非常高的要求,同时,药品的库存空间在医药库存中也有重要影响。首先针对快速失效的医药药品考虑了医药库存的合同保质期以及库存空间约束,同时考虑医院库存以及制造商库存,基于经济订货批量模型和经济生产批量模型建立了二级供应链的医药库存模型,然后用MATLAB软件求解了模型最优解,并对一些重要参数进行了敏感性分析。研究发现,合同保质期对医院订购批量、制造商生产批量和总库存成本有一定的影响,其中对于制造商的生产批量以及医院的库存成本影响较大。如果不考虑合同保质期的约束,将会对总库存成本带来更大损失。     

Evaluation of radiostability of some steroid derivatives

The effect of ionising radiation (15-100 kGy) on the physico-chemical properties of 6 steroid derivatives in solid state (Hydrocortisone, Hydrocortisone acetate, Prednisolone, Prednisolone acetate, Dexamethasone and Fludrocortisone acetate) was studied by differential scanning calorimetry (DSC), differential thermal analysis (DTA), scanning electron microscopy (SEM), UV spectrophotometry, high-performance liquid chromatography (HPLC), X-ray powder diffraction and polarimetry. DSC and DTA results revealed that the irradiated compounds undergo phase transitions at lower temperatures, show lower melting points and lower enthalpy of the melting process their non-irradiated analogues. The results of HPLC measurements proved a loss in the active substance content after irradiation ranging from 0.5 to 2.88%. No significant effect of irradiation was detected by the UV spectrophotometry or polarimetry in the course of the UV spectrum, absorbancy or optical rotation, as well as in the SEM photographs and X-ray patterns. For some compounds studied a correlation was found between the irradiation dose and the shifts in DSC curves and the loss of content determined by the HPLC method. Similar, but not so much pronounced relations were established in or earlier studies of the derivatives of nitroimidazole and 1,4-dihydropyridine. In general the results have shown relatively high radiochemical stability of the compounds studied and have proved that the DSC method is a sensitive detector of irradiation-caused changes in drugs in solid phase. This revised version was published online in July 2006 with corrections to the Cover Date.     

Enantioseparation of basic pharmaceutical compounds by capillary electrophoresis using sulfated cyclodextrins. Application to E-6006, a novel antidepressant

In this study, a chiral capillary electrophoresis method was optimized and validated for E-6006, a thienylpyrazolylethanamine derivative (pK_a 8.9). Enantioselectivity of neutral and anionic cyclodextrins (CDs) was evaluated at acid pH (3), obtaining cathodic and anodic migration, respectively. Hydroxypropyl-β-CD, carboxymethyl-β-CD and sulfobutyl ether-β-CD led to similar and partial selectivity, whereas sulfate (S)-β-CD produced baseline separation of the enantiomers. Four types of sulfated CDs were compared considering: cavity size (, β, γ) and random substitution versus unique derivative (S-β-CD, 6-heptakis-S-β-CD). Complete peak separation was obtained in all cases, but with different affinity and binding strength. Some factors that play a role in the complex formation include: position/region/degree of substitution, size of CD cavity and proportion of derivatives in mixtures. Enantioaffinity and enantioselectivity increased with the average of sulfate groups/mol. β Cavity size complexed better, although and γ cavities did not compromise separation. 6-Heptakis-S-β-CD had less affinity and separation efficiency, attributed to its lower degree and unique position of substitution. The method was optimized with S-β-CD (Aldrich, randomly substituted, 7–11 groups/mol). With this selector, the effect of pH value (3–9) was evaluated. Around pH 7 the cross-over point with change in the direction and order of migration was observed, associated with great enantioselectivity and long migration times. Fine tuning was done by adjusting the CD concentration and the buffer counterion. Definitive conditions were: uncoated silica capillary, 10 mM S-β-CD–25 mM sodium phosphate, pH 3. Validation parameters are included.