愈创维林那敏片中枸橼酸喷托维林的含量测定

目的 建立测定愈创维林那敏片中枸橼酸喷托维林含量的高效液相色谱(HPLC)法.方法 采用Agilent C18柱(150 mm ×4.6 mm,5 μm),流动相为0.05 mmol/L庚烷磺酸钠溶液(含三乙胺0.05%,用磷酸调pH至3.0)-甲醇(50:50),流速1 mL/min,检测波长210 nm,柱温30℃.结果 枸橼酸喷托维林质量浓度在10.08～100.8 mg/L的范围内与峰面积线性关系良好(r=0.999 9,n=6),平均回收率为99.87%,RSD=0.26%(n=9).结论 HPLC法灵敏、快速、准确,可用于愈创维林那敏片的枸橼酸喷托维林含量测定.     

HPLC测定复方氯丙那林鱼腥草素钠片的含量

目的建立同时测定复方氯丙那林鱼腥草素钠片中盐酸氯丙那林、马来酸氯苯那敏、盐酸溴己新含量的方法。方法采用HPLC法。色谱柱为Diamonsil C18(150 mm×4.6 mm,5μm),流动相为甲醇-水-三乙胺(50∶50∶0.5)(磷酸调pH3.0),检测波长212 nm。结果盐酸氯丙那林、马来酸氯苯那敏、盐酸溴己新分别在62.69~94.03、23.76~35.64、68.19~102.3μg.ml-1范围内呈良好的线性关系,平均回收率分别为100.0%、99.9%和99.6%(RSD均为0.3%)。结论该方法简便、快速、准确。     

HPLC—MS法测定人血浆中他林洛尔的浓度及其在中国健康志愿者体内的药动学研究

目的:建立一种快速、特异灵敏的测定人血浆中他林洛尔浓度的高效液相色谱-质谱法(HPLC-MS),为研究他林洛尔在中国健康志愿者体内的药物动力学研究提供手段。方法:以普萘洛尔作为内标(I.S.),血浆样品碱化后用叔丁基甲醚萃取,用 Phenomenex C_(18)反相色谱柱(4.6 mm×250 mm,5 μm,USA)进行分离,以乙腈-缓冲液(10 mmol·L~(-1)醋酸铵和0.1%甲酸)(40:60,v/v)为流动相,柱温40℃,流速0.85 mL·min~(-1),HPLC—MS/ESI~ 法选择性监测准分子离子峰(他林洛尔:m/z=364.3,I.S.:m/z=260.3)。结果:他林洛尔及内标普萘洛尔在5.5 min 内完全分离;他林洛尔在1.0～400.0 ng·mL~(-1)时线性关系良好,相关系数为0.9996;萃取回收率大于82%;方法回收率大于98%;最低检测浓度为0.3 ng·mL~(-1);日内日间 RSD均小于8%。主要药动学参数如下:C_(max)(147.8±63.8)ng·mL~(-1);t_(max)(2.0±0.7)h;t_(1/2)(12.0±2.6)h。结论:本方法简便快速,灵敏准确,适用于他林洛尔药物动力学的研究。     

高效液相色谱法检测大鼠血浆中盐酸环苯扎林浓度的方法研究

目的:建立血浆中盐酸环苯扎林含量的测定方法.方法:用高效液相色谱法(HPLC),色谱柱为Hypersil BDS-C18(5μm,4.6mm×250 mm),乙腈-0.085%磷酸水溶液(三乙胺调pH为6.5)65:35为流动相;流速为1.0mL·min-1;检测波长290 nm.结果:盐酸环苯扎林在12.06～241.2 ng·mL-1范围为内与峰面积线性关系良好(r=0.9998);对照品溶液48小时内稳定,RSD为1.1%;低、中、高3种血浆浓度的平均回收率为(94.45±5.21)%、(98.64±2.74)%和(99.62±1.36)%.结论:该方法简便,精密度及重现性均较好,分离效果好,该法适应于盐酸环苯扎林血浆样品的快速、大量分析.     

HPLC测定人血浆中的10α-甲氧基-6-甲基麦角林-8β-甲醇

目的 采用HPLC测定人血浆中尼麦角林主要代谢物10α-甲氧基-6-甲基麦角林-8β-甲醇(MDL)的血药浓度.方法 色谱柱为Luna C18柱(250 mm×4.6 mm,10 μm),流动相为乙腈-0.01 mol·L-1磷酸氢二钠(15:85,磷酸调pH3.5),流速为1.0 ml·min-1,柱温30℃,检测波长为225 nm.结果 线性范围为5.0～80.0 ng·ml-1(r=0. 9997,n=7),平均方法回收率分别为93.85%、94.83%、89.84%;日内RSD分别为4.93%、8.23%、10.63%(n=5),日间RSD分别为6.17%、6.13%、8.41%(n=5).结论 该法灵敏、简便、准确,适用于尼麦角林及相关制剂的临床研究.     

HPLC法测定盐酸氯丙那林片的含量和含量均匀度

目的:建立HPLC法测定盐酸氯丙那林片的含量和含量均匀度的方法。方法:采用岛津Shim-pack C_(18)色谱柱(4.6mm×150mm,5μm),流动相为甲醇-磷酸盐缓冲液(pH7.0)(6∶4),流速为1.0mL·min~(-1),检测波长为213nm。结果:盐酸氯丙那林在21～420μg·mL~(-1)浓度范围内呈良好线性关系(r=0.9999);平均回收率为100.2%,RSD为1.3%(n=9)。结论:该方法简便、可靠、准确,可用于该制剂的质量控制。     

高效液相色谱法测定复方枇杷喷托维林颗粒中枸橼酸喷托维林的含量

目的 建立复方枇杷喷托维林颗粒中枸橼酸喷托维林含量的高效液相测定方法.方法 采用Aglient C18(150 mm×4.6 mm,5 μm)色谱柱;流动相:1%三乙胺溶液(用磷酸调pH至3.0)-乙腈(70∶30);流速:1.0 mL·min-1;检测波长:210 nm.结果 枸橼酸喷托维林在0.02~1.01 g·L-1的质量浓度范围内线性关系良好,Y=6 652 832.11 X-8 399.71(r=0.999 9),平均加样回收率为99.4%,RSD=1.2%.结论 该法简便、准确,可用于复方枇杷喷托维林颗粒中枸橼酸喷托维林的质量控制.     

HPLC—MS法测定人血清中舍曲林的浓度

目的:建立人血清中盐酸舍曲林浓度的 HPLC-MS 法,用于其血药浓度测定并进行临床药动学和生物等效性研究。方法:300μL血清样品经乙腈沉淀后,以0.1%甲酸溶液-乙腈(40:60,v/v)为流动相,流速:0.2 mL·min~(-1),采用 Alltima-C_(18)柱(2.1 mm×100 mm,3.0μm)分离,通过气动辅助电喷雾离子化(ESI)方式,以选择离子反应监测(SRM)方式进行检测。18例健康志愿者按标准的2×2交叉试验方案设计,分别口服参比制剂及受试制剂各50 mg,用该法测定给药后不同时间点血清中舍曲林的浓度。结果:盐酸舍曲林浓度在0.6733～67.33 ng·mL~(-1)范围内呈良好的线性,低、中、高浓度的相对回收率分别为111.1%,94.68%,99.17%。该法被成功用于临床药代动力学和生物等效性研究。结论:该法灵敏、准确,适用于盐酸舍曲林的临床药动学和生物等效性研究。     

HPLC测定注射用尼麦角林的含量及其有关物质

目的建立测定注射用尼麦角林的含量及其有关物质的方法。方法采用HPLC法,Hypersil C18(250 mm×4.6 mm,10μm)为色谱柱,以甲醇-30 mmol.L-1NaH2PO4水溶液-三乙胺(60:40:0.8,磷酸调pH3.5)为流动相;检测波长287nm。结果尼麦角林在2.5~80.0μg.m l-1范围内,与峰面积的线性关系良好(r=0.9999);高、中、低3种浓度的平均回收率为99.3%,有关物质检查的限量为3.0%。结论所建方法准确、简便、快速,适用于注射用尼麦角林的质量控制。     

手性流动相添加RP-HPLC法测定盐酸舍曲林的含量和有关物质

目的:建立反相高效液相色潽法测定盐酸舍曲林的含量和有关物质。方法:采用Kromasil 100-5C8(250 mm×4.6 mm,5μm)色谱柱;流动相:混合缓冲液(磷酸二氢钠3.2 g、β-环糊精11.0 g、羟丙基-β-环糊精16.0 g加水至1 000 mL)-乙腈[65∶35,用10%H3PO4将pH值调至(3.0±0.2)];流速1.0 mL.min-1;检测波长218 nm;柱温:室温。结果:有关物质与盐酸舍曲林分离良好,盐酸舍曲林在0.074～0.740 mg.mL-1浓度范围内线性关系良好(r=0.999 9),平均回收率为98.5%(RSD=0.2%),有关物质检测限为2.0 ng(S/N=3)。结论:该方法操作简便、重复性好、专属性强,盐酸舍曲林异构体与主峰分离良好,可作为盐酸舍曲林片质量控制的依据。     

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.