奥沙普秦肠溶片在健康人体内的药动学

目的建立一种测定人体血浆中奥沙普秦含量的方法,并应用于奥沙普秦肠溶片的药动学研究。方法采用Agilent HPLC系统;色谱柱:Diamoniltm C18柱(150 mm×4．0 mm,5μm)。流动相为乙酸缓冲液(20 mmol·L-1,pH 4．0):甲醇=23:77,流速1．0 mL·min-1,λ=280 nm。结果奥沙普秦线性关系为Y=16．32×ρ-9．03(n=7,r=0．999 7);线性范围0．04～80 mg·L-1;最低检测限为0．012 mg·L-1;日内、日间RSD分别<5．05％、9．75％。结论本方法简便、准确、灵敏,可以作为奥沙普秦肠溶片血药浓度监测的有效方法。     

HPLC法同时测定复方氯霉素滴眼液中醋酸泼尼松龙、氯霉素及其降解产物氯霉素二醇物的含量

目的:建立同时测定复方氯霉素滴眼液中氯霉素、醋酸泼尼松龙及其降解产物氯霉素二醇物含量的方法。方法:采用高效液相色谱法。色谱柱为Dionex Acclaim C_(18),流动相为0.1%庚烷磺酸钠溶液-冰乙酸-乙腈-甲醇(60∶0.2∶30∶10,V/V/V/V),流速为1.0 mL/min,检测波长为271 nm,柱温为30℃,进样量为10μL。结果:氯霉素、醋酸泼尼松龙、氯霉素二醇物检测质量浓度线性范围分别为11.73~703.71μg/mL(r=0.999 8)、12.40~744.06μg/mL(r=0.999 8)、1.03~62.03μg/mL(r=0.999 8);氯霉素二醇物的定量限为0.01μg/mL;精密度、稳定性试验的RSD<2.0%;氯霉素、醋酸泼尼松龙重复性试验的RSD<2.0%,氯霉素二醇物的RSD=4.5%;回收率分别为100.6%~102.7%(RSD=0.60%,n=9)、97.5%~100.3%(RSD=0.80%,n=9)、100.0%~103.2%(RSD=1.10%,n=9)。结论:该方法结果准确、操作简便,可用于复方氯霉素滴眼液中氯霉素、醋酸泼尼松龙及其降解产物氯霉素二醇物含量的同时测定。     

HPLC法测定注射用泮托拉唑钠中的有关物质

目的:建立测定注射用泮托拉唑钠中有关物质的方法。方法:采用高效液相色谱法。色谱柱为Kromasil Hypersil ODS,流动相为0.01 mol/L磷酸氢二钾溶液(调节pH为7.0)-乙腈(梯度洗脱),流速为1.0 mL/min,检测波长为290 nm,柱温为40℃,进样量为20μL。结果:杂质A、B、C+E、D检测质量浓度线性范围分别为0.416 8~1.042 0μg/mL(r=0.999 8)、0.195 0~0.487 5μg/mL(r=0.999 9)、0.389 0~0.972 5μg/mL(r=0.999 8)、0.198 6~0.496 5μg/mL(r=0.999 8);定量限分别为0.834、0.780、1.556、0.794ng/mL,检测限分别为0.417、0.390、0.778、0.397 ng/mL;精密度试验的RSD<1.0%,重复性试验中总杂质峰面积的RSD<1.0%;回收率分别为98.81%~102.49%(RSD=1.18%,n=9)、95.31%~98.44%(RSD=0.91%,n=9)、96.88%~98.44%(RSD=0.52%,n=9)、97.87%~101.28%(RSD=1.05%,n=9)。结论:该方法简便、准确,可用于注射用泮托拉唑钠中有关物质的测定。     

2012—2014年上海市浦东新区周浦医院门急诊口服非甾体抗炎药的使用情况分析

目的分析上海市浦东新区周浦医院门急诊口服非甾体抗炎药(NSAIDs)的使用情况,为临床合理用药提供参考。方法对上海市浦东新区周浦医院2012—2014年门急诊的口服非甾体抗炎药的用药金额、用药频度(DDDs)、限定日费用(DDC)及药品排序比(B/A)等进行统计和分析。结果非甾体抗炎药的用药金额在2014年迅速增长;阿司匹林肠溶片、洛索洛芬钠胶囊和美洛昔康分散片的DDDs一直稳居前3位;塞来昔布胶囊的DDC在所有非甾体抗炎药中最高。B/A1.5的有酚氨咖敏片、阿司匹林肠溶片和安乃近片,B/A0.7的有塞来昔布胶囊、洛索洛芬钠片、奥沙普秦肠溶片和氨麻美敏片Ⅱ。结论上海市浦东新区周浦医院的非甾体抗炎药的使用基本合理,正朝着长效和低毒的新剂型方向发展。     

HPLC法测定盐酸氯卡色林原料药中的有关物质

目的:建立测定盐酸氯卡色林原料药中有关物质的方法。方法:采用高效液相色谱法。色谱柱为Welch ultimate XBODS,流动相为磷酸二氢钠溶液(pH为6.5)-乙腈(梯度洗脱),流速为1.0 mL/min,检测波长为220 nm,柱温为35℃,进样量为20μL。结果:杂质1、2、3检测质量浓度线性范围分别为0.075 60~7.560μg/mL(r=0.999 9)、0.081 40~8.140μg/mL(r=0.999 9)、0.099 24~9.924μg/mL(r=0.999 9);定量限分别为0.075 60、0.081 40、0.099 25μg/mL,检测限分别为0.022 68、0.024 42、0.02977μg/mL;精密度试验的RSD<2.0%,稳定性、重复性试验只检出杂质1,RSD<2.0%;回收率分别为98.53%~102.45%(RSD=1.06%,n=9)、98.26%~101.64%(RSD=1.03%,n=9)、100.08%~102.10%(RSD=0.70%,n=9)。结论:该方法灵敏、快速、准确、可靠,可用于盐酸氯卡色林原料药中有关物质的测定。     

UPLC-MS/MS法同时检测抗风湿中药制剂中非法添加的12种非甾体抗炎药

目的:建立同时检测抗风湿中药制剂中非法添加的12种非甾体抗炎药。方法:采用超高效液相色谱-质谱法。色谱条件:色谱柱为Hypersil Golden C18,流动相为5 mmol/L甲酸铵溶液-甲醇(梯度洗脱),流速为0.2 m L/min,柱温为40℃,进样量为2μL。质谱条件:离子源为电喷雾离子源,气帘气压为25 k Pa,雾化气压为60 k Pa,辅助气压为55 k Pa,电喷雾电压为4 500 V,离子源温度为650℃,采集方式为多反应监测模式。结果:对乙酰氨基酚、乙酰水杨酸、氨基比林、美洛昔康、布洛芬、萘普生、舒林酸、尼美舒利、双氯芬酸、吲哚美辛、酮洛芬、塞来昔布检测质量浓度线性范围分别为0.01~2.0μg/m L(r=0.995 6)、0.05~5.0μg/m L(r=0.997 6)、0.01~2.0μg/m L(r=0.998 7)、0.02~5.0μg/m L(r=0.995 0)、0.02~5.0μg/m L(r=0.995 3)、0.02~5.0μg/m L(r=0.996 5)、0.05~5.0μg/m L(r=0.995 4)、0.02~5.0μg/m L(r=0.996 0)、0.05~5.0μg/m L(r=0.995 9)、0.02~5.0μg/m L(r=0.9957)、0.02~5.0μg/m L(r=0.996 8)、0.01~2.0μg/m L(r=0.998 7);定量限≤0.20 mg/g,检测限≤0.05 mg/g;精密度、稳定性、重复性试验的RSD<5.0%;加样回收率为80.8%~114.2%(RSD为3.85%~7.32%,n=9)。结论:该方法操作简便,精密度、稳定性、重复性好,可用于抗风湿中药制剂中非法添加的12种非甾体抗炎药的同时检测。     

顶空气相色谱法同时测定艾司奥美拉唑镁原料药中6种有机溶剂的残留量

目的:建立同时测定艾司奥美拉唑镁原料药中甲醇、异丙醇、乙腈、二氯甲烷、乙酸乙酯、甲苯6种有机溶剂残留量的方法。方法:采用顶空气相色谱法。色谱柱为DB-624毛细管柱,程序升温,进样口温度为200℃,检测器为氢火焰离子化检测器,检测器温度为250℃,载气为氮气,氮气流速为2.0 mL/min,分流比为5∶1,顶空进样量为1 mL,顶空平衡温度为80℃,平衡时间为20 min。结果:甲醇、异丙醇、乙腈、二氯甲烷、乙酸乙酯、甲苯检测质量浓度线性范围分别为12.56~628.00μg/mL(r=0.999 7)、20.22~1 011.20μg/mL(r=0.999 9)、1.96~97.76μg/mL(r=0.999 7)、3.10~154.88μg/mL(r=0.999 8)、20.69~1 034.56μg/mL(r=0.999 8)、3.53~176.72μg/mL(r=0.999 8);定量限分别为1.00、0.91、0.47、0.93、0.41、0.35μg/mL,检测限分别为0.31、0.30、0.14、0.31、0.12、0.11μg/mL;精密度、稳定性、重复性试验的RSD<3%;加样回收率分别为94.53%~101.29%(RSD=2.15%,n=9)、97.78%~103.42%(RSD=1.77%,n=9)、96.99%~105.76%(RSD=2.59%,n=9)、96.83%~102.05%(RSD=1.86%,n=9)、97.98%~101.13%(RSD=0.88%,n=9)、97.80%~102.40%(RSD=1.41%,n=9)。结论:该方法灵敏、准确,可用于艾司奥美拉唑镁原料药中甲醇、异丙醇、乙腈、二氯甲烷、乙酸乙酯、甲苯6种有机溶剂残留量的同时测定。     

毛细管气相色谱法同时测定埃索美拉唑镁原料药中8种有机溶剂的残留量

目的:建立同时测定埃索美拉唑镁原料药中乙醇、乙酸乙酯、异丙苯、甲醇、甲苯、2-苯基-2-丙醇、二氯甲烷、乙腈8种有机溶剂残留量的方法。方法:采用毛细管气相色谱法。色谱柱为HP-1,程序升温,进样口温度220℃,检测器为氢火焰离子化检测器,检测器温度为250℃,载气为氮气,流速为4.0 mL/min,分流比为10∶1,进样量为1μL。结果:乙醇、乙酸乙酯、异丙苯、甲醇、甲苯、2-苯基-2-丙醇、二氯甲烷、乙腈检测质量浓度线性范围分别为45.2~904μg/mL(r=0.999 7)、45.5~909μg/mL(r=0.999 7)、9.0~180μg/mL(r=0.999 8)、27.1~542μg/mL(r=0.999 8)、8.7~174μg/mL(r=0.999 7)、9.1~183μg/mL(r=0.999 4)、5.8~115μg/mL(r=0.999 4)、3.7~74μg/mL(r=0.999 4);定量限分别为4.5、3.0、1.4、2.7、0.6、3.0、3.9、2.8 ng,检测限分别为2.2、1.0、0.4、1.4、0.3、1.0、2.0、1.4 ng;精密度试验的RSD<2.0%,重复性试验中只检出乙醇、甲醇、甲苯,其峰面积的RSD均<2.0%;加样回收率分别为95.6%~104.9%(RSD=3.3%,n=9)、98.7%~102.0%(RSD=1.1%,n=9)、100.0%~103.1%(RSD=1.1%,n=9)、95.7%~104.4%(RSD=3.0%,n=9)、99.3%~104.4%(RSD=1.7%,n=9)、95.6%~102.2%(RSD=2.6%,n=9)、95.1%~103.3%(RSD=2.6%,n=9)、97.5%~103.3%(RSD=1.7%,n=9)。结论:该方法灵敏度好、操作简单,适用于埃索美拉唑镁原料药中8种有机溶剂残留量的同时测定。     

HPLC法测定奥沙普秦肠溶片的含量

目的 建立高效液相色谱法测定奥沙普秦肠溶片的含量.方法 采用高效液相色谱法,色谱条件:SHIMADZU shim-pack C18色谱柱;流动相:乙腈水(磷酸调节pH至2.5,50∶50):检测波长:286nm;流速:1.0 mL·min1.结果 奥沙普秦在4.224～105.6 μg·mL-1的浓度范围内与峰面积呈良好的线性关系(r=0.999 9),最低检出限为0.02 μg·mL-1,回收率为99.9％,RSD为0.3％.结论 本方法专属性好、准确、灵敏,适用于奥沙普秦肠溶片的含量测定.     

离子抑制色谱法测定伊班膦酸钠原料药中的有关物质

目的:采用离子抑制色谱法测定伊班膦酸钠原料药中的有关物质。方法:色谱柱为Dionex IonPac AS11-HC,流动相为氢氧化钾溶液(梯度洗脱),流速为1.1 mL/min,柱温为45℃,进样量为20μL,检测器为抑制型电导检测器,检测器温度为35℃。结果:亚磷酸盐、杂质Ⅰ、磷酸盐检测质量浓度线性范围分别为3.08~30.83μg/mL(r=0.999 9)、2.84~28.43μg/mL(r=0.999 1)、2.95~29.52μg/mL(r=0.999 9);定量限分别为2.47、56.7、3.31 ng,检测限分别为0.75、17.2、1.0 ng;精密度、稳定性、重复性试验的RSD<4.0%;加样回收率分别为101.49%~103.57%(RSD=0.7%,n=9)、100.00%~104.85%(RSD=1.8%,n=9)、101.35%~104.08%(RSD=0.9%,n=9)。结论:该方法简便、准确、灵敏,适用于测定伊班膦酸钠原料药中的有关物质。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.