双波长法测定凝胶剂中甲磺酸帕珠沙星的含量

目的：建立甲磺酸帕珠沙星凝胶中甲磺酸帕珠沙星含量的测定方法。方法：采用双波长紫外分光光度法,测定波长为247nm,参比波长为232nm,测得吸收度差值（ΔA）为定量依据。结果：甲磺酸帕珠沙星在3～10μg/ml浓度范围内线性良好,相关系数为0.9993,平均加样回收率为100.3%,RSD为1.4%（n=9）。结论：本方法测定甲磺酸帕珠沙星凝胶的含量,可消除辅料的干扰,其方法简便、快速、准确。     

HPLC法测定甲磺酸帕珠沙星原料及其制剂含量

目的:采用高效液相色谱法测定甲磺酸帕珠沙星原料及其制剂含量.方法:Hypersil C18(5 μm,4.6 mm×250 mm)色谱柱,0.1%磷酸溶液(加磷酸氢二钾80.5 mg)-乙腈(85:15)为流动相,流速1.0ml·min-1,柱温30℃,检测波长243 nm.结果:甲磺酸帕珠沙星在5～500μg·ml-1内与峰面积呈良好的线性关系.甲磺酸帕珠沙星原料(3批)加样回收率99.2%甲磺酸帕珠沙星注射液加样回收率均值为100.1%;甲磺酸帕珠沙星氯化钠注射液加样回收率均值为99.7%.结论:采用HPLC测定原料及其制剂中甲磺酸帕珠沙星含量方法简便,结果可靠.     

反相高效液相色谱法测定血浆中的帕珠沙星

目的:建立反相高效液相色谱法测定人血浆中帕珠沙星浓度,用于帕珠沙星人体药动学研究.方法:采用YMC C18(150 mm×4.6 mm,5 μm)色谱柱,柱温为35℃,流动相为乙腈-0.025 mol·L-1醋酸钠(醋酸调pH 2.6)(13:87),流速为1 mL·min-1.以盐酸芦氟沙星为内标,检测波长249 nm.结果:标准曲线线性范围78.125～2 000μg·mL-1;萃取回收率66.76%～72.76%;方法回收率97.85%～110.9%;日内RSD在5.1%～9.9%;日间RSD在4.8%～6.2%.结论:本方法快速、灵敏、准确、简便,适用于帕珠沙星血药浓度测定及药动学研究.     

高效液相色谱法同时测定大鼠甲磺酸帕珠沙星和头孢哌酮的血浆浓度

目的建立大鼠甲磺酸帕珠沙星和头孢哌酮血浆浓度的反相高效液相色谱分析方法,为研究药物相互作用及联合用药后的药动学参数提供测定方法.方法用高氯酸沉淀血浆蛋白,采用Hypersil BDS C18柱(4.6 mm×150 mm,5 μm),流动相为乙腈-磷酸三乙胺水溶液(0.5%磷酸,1%三乙胺)(17∶83,v/v),检测波长为245 nm.结果甲磺酸帕珠沙星在0.1～100mg·L-1,头孢哌酮在0.5～500 mg·L-1,峰面积与浓度呈良好线性关系(r1=0.999 6,r2=0.999 7),平均绝对回收率为99.3%和105.4%,平均相对回收率为104.2%和98.6%,日内、日间RSD均小于10%.结论本方法操作简便,专属性及重现性好,适用于进一步的药物相互作用及体内药动学研究.     

反相高效液相色谱法测定人血浆及尿液中甲磺酸帕珠沙星浓度

目的:建立血浆及尿液中甲磺酸帕珠沙星浓度的反相高效液相色谱分析方法。方法:用甲醇沉淀血浆蛋白,离心后取上清液进行色谱分析;尿样稀释后离心取上清液进样。分析柱为DiamonsilC18,流动相为乙腈-0.05mol/L磷酸二氢钾(含1%四丁基溴化铵)(8∶92,V/V),流速为1.4ml/min,激发波长320nm,发射波长400nm。结果:甲磺酸帕珠沙星在血浆和尿液中的检测浓度线性范围均为31.25～10000ng/ml(r=0.9999);在血浆、尿液中的相对回收率分别为97.77%～99.87%、98.31%～100.82%,RSD<1.0%～3.0%。结论:本方法准确可靠、操作简便,适用于甲磺酸帕珠沙星的临床药动学及常规血药浓度监测。     

RP-HPLC法测定甲磺酸帕珠沙星及有关物质

目的建立甲磺酸帕珠沙星的RP-HPLC含量测定及有关物质检测方法.方法采用C18柱(5μm,4.6mm×250mm),流动相为乙腈-磷酸三乙胺水溶液(含0.5%磷酸,1%三乙胺)(5248),检测波长为254nm.结果甲磺酸帕珠沙星在1.0～200μg@mL-1浓度范围内,峰面积与浓度呈良好线性关系(r=0.9997),平均回收率为(99.3±0.56)%.结论本法简便,专属性及重现性好,可用于测定甲磺酸帕珠沙星含量及有关物质.     

HPLC测定人血浆中帕珠沙星浓度

目的建立测定人血浆中帕珠沙星浓度的高效液相色谱法。方法血浆样品用10%高氯酸沉淀蛋白。色谱柱为Diamonsil C18柱(200mm×4.6mm,5μm),流动相为0.02mol·L-1磷酸二氢钠溶液(含三乙胺0.5%,用磷酸调至pH3.0)-乙腈(82∶18),流速为1.0mL·min-1,紫外检测波长245nm。结果血浆中内源性物质对样品测定无干扰。本方法线性范围为0.05～50μg·mL-1(r=0.9999),最低定量浓度为0.05μg·mL-1,提取回收率大于80%,方法回收率为100.6%～101.4%,日内、日间RSD均小于6%。结论本法简便、灵敏、准确,适用于帕珠沙星药动学的研究。     

高效液相色谱法同时测定帕珠沙星和氨茶碱的含量

目的:建立同时测定帕珠沙星和氨茶碱含量的HPLC方法,并考察两种药物配伍后的稳定性。方法:分析柱为shimpackC18柱(150mm×4.6mm);流动相为磷酸二氢钾缓冲液-甲醇(17∶10),用磷酸调pH至3.7;检测波长为239nm。结果:帕珠沙星线性范围为0.5~5.0mg.L-1(r=0.9997)。相对回收率为101.4%;茶碱线性范围为1.0~20.0mg.L-1(r=0.9998)。相对回收率为100.2%。结论:以HPLC法用甲醇做溶剂可同时测定帕珠沙星与氨茶碱的含量。该方法简便、准确、灵敏。     

HPLC法测定甲磺酸帕珠沙星注射液中帕珠沙星的含量

目的 建立高效液相色谱法测定帕珠沙星的含量.方法 采用Hypersil ODS2 4.6×200 mm,5μm(依利特)柱,以乙腈-0.67%磷酸二氢钾溶液(用磷酸调节pH值至2.2)-0.05mol·L-1四丁基溴化铵溶液(50 ∶ 432 ∶ 25)为流动相,流速为1.0ml·min-1,紫外检测波长320nm.结果 帕珠沙星在进样量为0.9756～9.756μg范围内呈良好线性关系(r=0.99998,n=6),平均回收率为100.2%,RSD=0.2%(n=9).结论 采用HPLC法测定帕珠沙星的含量,方法简便快速,结果准确,可作为甲磺酸帕珠沙星制剂的质量控制方法.     

高效液相色谱法测定人血浆中甲磺酸帕珠沙星浓度

目的建立人血浆中甲磺酸帕珠沙星(PZX)浓度的测定方法。方法采用蛋白沉淀法处理血样,以高效液相色谱法测定。流动相乙腈-0.05mol·L-1KH2PO4(20∶80,v/v);检测波长245nm;流速1.0ml·min-1。结果线性范围0.1～15.0μg·ml-1(r=0.9999),平均提取回收率为98.6%,日内、日间RSD均<8.47%。结论本法测定人血浆中PZX浓度简便快捷,灵敏度高,重复性好,适用于人体药动学研究。     

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.