尼美舒利干混悬剂含量测定方法研究

目的建立尼美舒利干混悬剂含量测定方法。方法色谱柱为迪玛C18柱(250mm×4.6mm,5μm);流动相为0.1%的磷酸溶液(用氨水调节pH值至7.0)-乙腈(60∶40);检测波长为298nm;流速1mL/min;柱温30℃;进样量20μL。结果尼美舒利在0.856～85.60μg/mL质量浓度范围内线型关系良好,r=0.9999(n=7),平均回收率为100.3%,RSD为0.54%。结论方法操作简便,结果准确,可用于尼美舒利干混悬剂的含量测定。     

反相高效液相色谱法测定尼美舒利分散片的含量

目的建立测定尼美舒利分散片含量的反相高效液相色谱法。方法采用LBondapak C18色谱柱(300 mm×4.0 mm,5μm),乙腈-水(45∶55)为流动相,柱温为25℃,检测波长为254 nm,流速为1.0 mL/min。结果尼美舒利质量浓度在40～200μg/mL范围内与峰面积线性关系良好(r=0.9999),平均回收率为99.60%,RSD为0.47%(n=6)。结论该方法简便、快速、准确、灵敏度高、重复性好,可用于尼美舒利分散片含量的测定。     

Development and validation of an HPLC assay for the quantitation of mefunidone,a novel derivative of pirfenidone,and an initial pharmacokinetics study in liver microsomes

本研究开发了一种简单可靠的HPLC-UV方法用于美氟尼酮的测定。生物分析步骤包括从500 μL肝微粒体系统中通过甲醇沉淀蛋白质提取美氟尼酮。色谱条件:色谱柱为Agilent TC-C₁₈柱(4.6 mm×250 mm, 5 μm), 流动相为10 mM甲酸铵(用10%的甲酸调PH至2.9)–乙腈(70:30, v/v),流速为1.0 mL/min, UV检测波长设定在245 nm。美氟尼酮和吡非尼酮(内标物)分别在6.0和9.7分钟洗脱,总运行时间为12分钟。根据美国食品和药物管理局生物分析指南,进行了方法验证,结果符合验收标准。美氟尼酮在肝微粒体中的标准曲线在0.5–16 μg/mL范围内呈线性关系。美氟尼酮内和外间精确度低于9.0％,偏差在±10.0％以内。美氟尼酮在肝微粒体中孵育后,该方法成功应用于药代动力学研究。     

液相色谱-串联质谱法检测人血浆中尼美舒利及其代谢物的浓度

目的 建立一种同时检测人血浆中尼美舒利及其代谢物4-羟基尼美舒利的液相色谱-串联质谱方法。方法 以非那西汀为内标,用乙腈沉淀蛋白法对人血浆样品进行处理。用Restek Allure PFP Propyl(100.0 mm×2.1 mm, 5μm)液相色谱柱分离,流动相为0.1%甲酸和0.1%甲酸-乙腈溶液,流速为0.2 mL·min^-1。用电喷雾离子源(ESI源),负离子多反应监测模式。考察该方法的专属性、标准曲线与定量下限、精密度与回收率、稳定性和基质效应。结果 血浆中尼美舒利及4-羟基尼美舒利均在10.0～1 000.0 ng·mL^-1内线性关系良好,相关系数均>0.997 0,最低定量限均为10.0 ng·mL^-1,绝对回收率均>80%,日内、日间RSD均小于10.15%。结论 本方法操作简便、准确性好、灵敏度高,适用于人血浆中尼美舒利及其代谢物浓度的分析。     

LC-MS法测定人血浆中尼美舒利的浓度

目的:建立以液-质联用法测定人血浆中尼美舒利浓度的方法。方法:色谱柱为Agilent Zorbox SB-Cl8,流动相为乙腈-0.1%甲酸(65∶35),流速为1.0mL·min-1,柱温为35℃,内标为缬沙坦;正离子检测模式,选择m/z309(尼美舒利,[M+H]+)和m/z436(缬沙坦,[M+H]+)进行监测。结果:尼美舒利血药浓度在5～50ng·mL-1范围内线性关系良好(r=0.9989);方法回收率为87.1%～92.9%;日内、日间RSD分别为3.1%～5.8%、6.4%～9.2%。结论:本方法灵敏、简便,结果准确可靠,重复性好,可用于尼美舒利的临床血药浓度监测和药动学研究。     

高效液相色谱法测定布美他尼注射液的含量

目的建立高效液相色谱法测定布美他尼注射液的含量。方法采用Hypersil ODS2柱(4.6mm×250mm,5μm),检测波长328nm,流动相为甲醇-水(75∶25),流速为1.0mL·min-1。结果布美他尼在29.016μg·mL-1~67.704μg·mL-1浓度范围内与峰面积呈良好线性关系(r=0.9999),平均回收率为99.8%,RSD为1.38%(n=9)。结论该方法操作简便,结果准确,重现性好。     

尼美舒利颗粒剂的溶出度方法研究

目的 建立尼美舒利颗粒剂溶出度的测定方法.方法 采用浆法,以磷酸缓冲液(pH8.0)为溶出介质;溶出量采用高效液相色谱的方法测定.以Diamond C18柱(250 mm×4.6 mm,5 μm),流动相为0.1%磷酸溶液-甲醇(45∶55),流速为1 mL·min-1,检测波长299 nm.结果 在15 min内不同厂家生产的尼美舒利颗粒剂的溶出度均能达到75%.结论 方法简单,准确可靠,可用于尼美舒利颗粒剂的溶出度测定.     

高效液相色谱法测定布美他尼片的溶出度

目的:建立高效液相色谱法测定布美他尼片的溶出度。方法:采用 Alltima C_8色谱柱(4.6 mm×250 mm,5μm),流动相为磷酸盐缓冲液(pH=7.8)-乙腈(70:30),流速1.0 mL·min~(-1),紫外检测波长为216 nm,进样体积为20μL。结果:布美他尼在0.6～1.6μg·mL~(-1)范围内浓度与峰面积呈良好线性关系(r=0.9998);高、中、低3种不同浓度的平均回收率范围为99.0～103.0%;最低检测量为0.01 ng。结论:本法操作简便、准确、专属性强,可满足布美他尼片溶出度质量控制的要求。     

HPLC-MS/MS法用于达沙替尼血药浓度监测

目的 建立一种稳定性好、灵敏度高、通用性强测定人血浆中达沙替尼血药浓度的高效液相色谱-串联质谱(HPLC-MS/MS)检测方法。方法 血浆样本经甲醇除蛋白后,流动相为含0.1%甲酸的甲酸铵缓冲液(A相)和0.1%甲酸的乙腈溶液(B相),采用梯度洗脱方式,Luna^? C₁₈色谱柱(2.0 mm×20 mm, 3μm)进行分离,流速为0.6 mL·min^-1,柱温35℃。电喷雾离子源(ESI),正离子模式,多反应监测,类似物伊马替尼-D₈作为内标。用于定量分析的离子对为m/z 488.2→m/z 401.1 (达沙替尼)和m/z 502.3→m/z 394.1(伊马替尼-D₈)。结果 达沙替尼的线性范围为1～1000 ng·mL^-1,定量下限为1 ng·mL^-1;日内及日间相对标准偏差(RSD)均小于10%,达沙替尼低、中、高浓度的提取回收率分别为97.8%,98.6%,94.1%。临床样本检测结果表明中国慢性髓系白血病患者达沙替尼血药浓...     

高效液相色谱法测定布美他尼片的含量

目的建立高效液相色谱法测定布美他尼片的含量。方法采用Hypersil ODS2柱(4.6mm×250mm,5μm),检测波长328nm,流动相为甲醇-水(75∶25),流速为1.0m l.m in-1。结果布美他尼进样量在0.208μg~1.040μg范围内与峰面积呈良好线性关系(r=0.9999),平均回收率为100.04%,RSD为1.41(n=9)。结论该方法操作简便、结果准确、重现性好。     

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.     

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.     

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.