苦参炭薄层色谱鉴别研究

目的：研究苦参炭的薄层色谱鉴别。方法选用甲苯-丙酮-甲醇（8：3：1.5）为展开剂,浓氨水饱和,碘化铋钾试液为显色剂,以苦参碱、槐定碱、氧化苦参碱为对照品进行薄层鉴别。结果选用甲苯-丙酮-甲醇（8：3：1.5）为展开剂,碘化铋钾试液为显色剂进行薄层鉴别,色谱斑点清晰,能有效提供鉴别特征。结论方法可行,为建立完整、科学的苦参炭质量标准提供了参考依据。     

气相色谱法测定氢溴酸替格列汀中溴乙烷残留量

目的 建立氢溴酸替格列汀中遗传毒性杂质溴乙烷残留量的气相色谱（GC）检测方法。方法 采用迪马DM-624色谱柱（30 m×0.53 mm×3.0 μm）;电子捕获检测器（ECD）;程序升温：初始柱温40 ℃,保持3 min,以20 ℃/min升温至200 ℃,保持5 min;进样口温度：210 ℃;检测器温度：210 ℃;载气：氮气;分流比：3：1;进样量1 μL。结果 溴乙烷在0.75～6.75 μg/mL与峰面积呈良好的线性关系（r=0.999 7）,最低检测限为0.26 μg/mL。平均回收率为99.4%,RSD值为0.3%（n=9）。3批氢溴酸替格列汀样品中均未检测出溴乙烷。结论 该方法简便、准确,重复性好,适用于氢溴酸替格列汀中溴乙烷残留量的控制。     

Structural and Binding Studies of SAP-1 Protein With Heparin

SAP-1 is a low molecular weight cysteine protease inhibitor (CPI) which belongs to type-2 cystatins family. SAP-1 protein purified from human seminal plasma (HuSP) has been shown to inhibit cysteine and serine proteases and exhibit interesting biological properties, including high temperature and pH stability. Heparin is a naturally occurring glycosaminoglycan (with varied chain length) which interacts with a number of proteins and regulates multiple steps in different biological processes. As an anticoagulant, heparin enhances inhibition of thrombin by the serpin antithrombin III. Therefore, we have employed surface plasmon resonance (SPR) to improve our understanding of the binding interaction between heparin and SAP-1 (protease inhibitor). SPR data suggest that SAP-1 binds to heparin with a significant affinity (K_D = 158 nm ). SPR solution competition studies using heparin oligosaccharides showed that the binding of SAP-1 to heparin is dependent on chain length. Large oligosaccharides show strong binding affinity for SAP-1. Further to get insight into the structural aspect of interactions between SAP-1 and heparin, we used modelled structure of the SAP-1 and docked with heparin and heparin-derived polysaccharides. The results suggest that a positively charged residue lysine plays important role in these interactions. Such information should improve our understanding of how heparin, present in the reproductive tract, regulates cystatins activity.     

Molecular design opportunities presented by solvent-exposed regions of target proteins

Solvent-exposed regions, or solvent-filled pockets, within or adjacent to the ligand-binding sites of drug-target proteins provide opportunities for substantial modifications of existing small-molecular drug molecules without serious loss of activity. In this review, we present recent selected examples of exploitation of solvent-exposed regions of proteins in drug design and development from the recent medicinal-chemistry literature.     

饮用水中多种有机磷农药残留的气相色谱-三重四极杆质谱测定法

目的建立一种同时测定饮用水中7种有机磷农药残留量的气相色谱-三重四极杆质谱（GC-MS/MS）方法。方法采用液-液萃取方法,用二氯甲烷对水样中7种有机磷农药进行提取,无水硫酸钠脱水,滤液在40℃水浴中旋转蒸发近干,用二氯甲烷定容,GC-MS/MS测定,外标法定量。结果 7种有机磷农药在21 min内分离,在0.01-10 mg/L范围内相关系数r2均在0.99以上,在0.05、0.25和0.45 mg/L 3个水平加标回收率在78.9%-99.3%之间,相对标准偏差均小于10%,检出限为0.02-0.06μg/L。结论该方法操作简单,准确度和精密度高,消除了其他有机磷农药的干扰,避免假阳性的出现,适用于饮用水中7种有机磷农药残留量的检测和确证。     

气相色谱法测定氧化白藜芦醇中的4种残留溶剂

摘要 目的：建立氧化白藜芦醇中叔丁醇、乙醇、乙酸乙酯、乙二醇4种有机溶剂残留量的测定方法。方法：以DB-624弹性石英毛细管柱为色谱柱（30 m×0.32 mm,1.8 μm）,采用氢火焰离子化检测器,载气为氮气,进样口温度为250 ℃,检测器温度为300 ℃,柱温采用程序升温（70 ℃保持3 min,以30 ℃/min的速率升温至100 ℃,保持8 min,然后以30 ℃/min的速率升温至210 ℃）,流速为3 mL?min-1。以 N,N-二甲基甲酰胺为溶剂,进样体积为1 μL。结果：4种有机溶剂均能得到很好的分离。叔丁醇、乙醇、乙酸乙酯、乙二醇检测质量浓度线性范围分别为395.28～1 482.3 μg?mL-1（r＝0.999 9）、398.16～1 493.1 μg?mL-1（r＝0.999 9）、395.84～1 484.4 μg?mL-1（r＝0.999 9）、53.12～199.2 μg?mL-1（r＝0.999 6）;定量限分别为9.88、19.91、19.79、53.12 μg?mL-1,检测限分别为3.95、9.95、9.90、19.92 μg?mL-1;精密度、重复性和稳定性的RSD均小于5.0％;乙醇、叔丁醇、乙酸乙酯和乙二醇平均回收率（n =9）分别为100.81%、96.72%、99.14%、99.51%,RSD分别为2.93%、3.98%、2.75%、3.34%,且精密度较好。测定样品三批,样品中叔丁醇的残留量分别为 0.03%,0.12% 和0.02%,乙醇、乙酸乙酯和乙二醇均未被检测到。结论：本文经方法学验证可用于氧化白藜芦醇中4种残留溶剂的分离与测定。     

Freeze-Drying From Organic Co-Solvent Systems,Part 2: Process Modifications to Reduce Residual Solvent Levels and Improve Product Quality Attributes

The use of co-solvent systems can benefit the freeze-drying process and product performance. In this study, cycle designs were applied based on existing recommendations for water-based formulations. Modifications thereof and the influence on the process (e.g., drying times) and product quality attributes (e.g., product appearance, residual solvent) were tested for various cosolvent systems. It was found that fast freezing was associated with the formation of large crystals for 50 mg/g polyvinylpyrrolidone in 40% 1,4-dioxane (w/w), resulting in a 7% reduction of primary drying. The application of high shelf temperatures during primary drying for 50 mg/g polyvinylpyrrolidone in 70% tert-butanol was feasible, resulting in shorter primary drying times but high residual solvent levels (7.7%). Most notable was that the inclusion of an evaporation step after freezing improved the product appearance for low-melting co-solvents (10% ethanol and 10% acetone). No ice or solvent nucleation occurred in the case of 50 mg/g mannitol in 50% N,N-dimethylacetamide during the normal freezing stage. Instead, the solution viscosity significantly increased after cooling to low shelf temperatures, followed by product evaporation (rather than sublimation) during the drying phase and failure to form a product cake after drying. The application of annealing enabled nucleation and sublimation.     

A Nonionic Polyethylene Oxide (PEO) Surfactant Model: Experimental and Molecular Dynamics Studies of Kolliphor EL

Polyethoxylated, nonionic surfactants are important constituents of many drug formulations, including lipid-based formulations. In an effort to better understand the behavior of formulation excipients at the molecular level, we have developed molecular dynamics (MD) models for the widely used surfactant Kolliphor EL (KOL), a triricinoleate ester of ethoxylated glycerol. In this work, we have developed models based on a single, representative molecular component modeled with 2 force field variations based on the GROMOS 53A6_DBW and 2016H66 force field parameters for polyethoxylate chains. To compare the computational models to experimental measurements, we investigated the phase behavior of KOL using nephelometry, dynamic light scattering, cross-polarized microscopy, small-angle X-ray scattering, and cryogenic transmission electron microscopy. The potential for digestion of KOL was also evaluated using an in vitro digestion experiment. We found that the size and spherical morphology of the KOL colloids at low concentrations was reproduced by the MD models as well as the growing interactions between the aggregates to from rod-like structures at high concentrations. We believe that this model reproduces the phase behavior of KOL relevant to drug absorption and that it can be used in whole formulation simulations to accelerate the formulation development.     

Enhancing the Pharmaceutical Behavior of Nateglinide by Cocrystallization: Physicochemical Assessment of Cocrystal Formation and Informed Use of Differential Scanning Calorimetry for Its Quantitative Characterization

The aim of this study was to synthetize cocrystals of nateglinide, an antidiabetic agent of biopharmaceutics classification system Class IIa, as a strategy to improve both the solubility and the dissolution rate of the drug. Benzamide was selected by a screening procedure as a suitable coformer, and binary mixtures with different compositions were prepared and analyzed by differential scanning calorimetry (DSC). An in-depth analysis of DSC data allowed obtaining both the eutectic mixture and cocrystal compositions. The rationale of such an analysis was highlighted and explained. Cocrystals were prepared by kneading and solvent evaporation. Their formation was proved by DSC and confirmed by X-ray powder diffraction, solid-state nuclear magnetic resonance, and Fourier-transform infrared spectroscopy. The functional groups involved in the interaction leading to cocrystals formation were investigated by spectroscopic techniques. The in vitro dissolution profiles show that cocrystals have definite better pharmaceutical performances than the pure drug.     

19种粉剂抗生素溶解后体积的研究

目的观察粉剂抗生素溶解后体积的变化,提高给药剂量的准确性。方法收集19种常用粉剂抗生素,溶入10mL相应溶媒,充分溶解后记录体积的变化情况。结果18种抗生素溶解后体积增加,其中11种增量5%以上,5种增量10%以上,最多增量达3mL。结论临床护士应注意粉剂抗生素溶解后体积变化对注射剂量准确性的影响,加强给药护理的环节管理,确保给药剂量的准确性。