中国西部健康人群口服恩曲他滨胶囊的药动学

目的:建立固相萃取-高效液相色谱法测定人血浆中恩曲他滨含量的方法,并研究口服恩曲他滨胶囊在中国西部健康人群的药动学特征。方法:以拉米夫定为内标,选择固相萃取柱提取样品,在分离柱上,以甲醇-含0.08%三乙胺的20mmol.L-1磷酸二氢钾水溶液(稀磷酸调pH3.5)为流动相,采用梯度洗脱,检测波长为279 nm。结果:血浆中内源性物质对恩曲他滨的测定无干扰,最低检出限为7 ng.mL-1,恩曲他滨在10～5 000 ng.mL-1范围内线性关系良好,r=0.999 8。绝对回收率为93.5%～96.7%,方法回收率为93.1%～97.6%,日内精密度RSD≤6.1%,日间精密度RSD≤7.4%。结论:本方法处理简单,无干扰,灵敏度高,中国西部人群单独给予恩曲他滨胶囊的的血浆半衰期明显缩短,替诺福韦和高脂食物使得恩曲他滨血浆浓度的达峰时间明显延迟,其他药动学参数基本不变。     

盐酸纳洛酮中有机溶剂残留量的毛细管GC测定

建立盐酸纳洛酮原料中多种有机溶剂残留量的分离测定方法.采用气相色谱法,载气为氮气,FID检测器,色谱柱为HP-50毛细管柱,程序升温,外标法测定盐酸纳洛酮中乙醇、丙酮、二氯甲烷、乙酸乙酯、甲苯的残留量.5种有机溶剂完全分离,在所考察的浓度范围内具有良好的线性,r为0.9998～0.9999,平均回收率为96.6%～101.9%,精密度RSD均小于10%,检测限为0.10～0.19μg·mL-1.本方法快速、灵敏、准确,适用于盐酸纳洛酮中多种有机溶剂残留量的测定.     

顶空气相色谱法测定盐酸格拉司琼中多种有机溶剂残留量

建立盐酸格拉司琼原料中多种有机溶剂残留量的分离测定方法.采用顶空气相色谱法,载气为氮气,FID检测器,色谱柱为HP-1毛细管柱,程序升温,外标法测定盐酸格拉司琼中甲醇、异丙醇、乙醚、二氯甲烷、氯仿、四氢呋喃、二甲基甲酰胺、甲苯的残留量.8种有机溶剂完全分离,在所考察的浓度范围内具有良好的线性,r为0.9988～0.9997,平均回收率为93.5%～103.1%,精密度RSD均小于10%,检测限为0.003～1.15μg.ml-1.本方法快速、灵敏、准确,适用于盐酸格拉司琼中多种有机溶剂残留量的测定.     

顶空气相色谱法测定甲磺酸帕珠沙星中多种残留溶剂

目的 建立甲磺酸帕珠沙星原料中多种有机溶剂残留量的分离测定方法.方法 采用顶空气相色谱法,载气为氮气,FID检测器,色谱柱为HP-INNOWax毛细管柱,程序升温,以外标法测定了甲磺酸帕珠沙星中乙醚、乙酸乙酯、乙醇、二氧六环、二甲基甲酰胺的残留量.结果 5种有机溶剂完全分离,在所考察的浓度范围内具有良好的线性关系,r为0.999 1～0.999 8,平均回收率为91.5%～102.5%,精密度RSD均小于10%,检测限为0.02～0.8μg/mL.结论 所用方法快速、灵敏、准确,适用于甲磺酸帕珠沙星中多种有机溶剂残留量的测定.     

恩曲他滨分散片的人体生物等效性试验研究

目的研究恩曲他滨分散片在健康志愿者体内的相对生物利用度。方法采用标准二阶段交叉设计(Two-peri-od Crossover Design)自身对照试验方法。血药浓度测定采用高效液相色谱法。结果单次口服200mg恩曲他滨分散片和恩曲他滨胶囊的t1/2分别为4.41±1.66h,4.25±1.75h,Tmax分别为0.77±0.2h、0.94±0.25h,Cmax分别为2345.82±680.61ng.mL-1、2290.47±722.08ng.mL-1,AUC(0~24h)分别为10330.91±3105.55ng.h.mL-1、9751.35±2622.75ng.h.mL-1。试验过程中未观察到药物不良反应发生。结论恩曲他滨分散片对Gilead Science公司生产的Emtriva(恩曲他滨胶囊)的相对生物利用度为105.4%,两种恩曲他滨制剂在人体内具有生物等效性。     

非氘代溶剂在氟核磁共振定量中的应用

目的 建立使用非氘代溶剂的氟核磁共振定量方法。方法 以氟化钠为内标、恩曲他滨为样品、去离子水为溶剂,测定氟核磁共振谱,进行线性关系考察、精密度试验、稳定性试验、耐用性试验;平行配制5份样品,进样测定,通过样品响应信号与内标响应信号面积比值,计算恩曲他滨含量;同时利用质量平衡法测定恩曲他滨的含量,两种方法进行比较。结果 非氘代溶剂的氟核磁共振谱图中氟化钠与恩曲他滨响应信号分离较远,互不干扰;方法线性关系良好,精密度、稳定性、耐用性均符合要求;氟核磁共振测定样品中恩曲他滨平均质量分数为100.1%,RSD值为0.57%,与质量平衡法测定结果99.7%基本一致。结论 建立的氟核磁定量方法无需使用氘代溶剂,准确快速,可以有效降低试验成本及环境污染。     

顶空气相色谱法测定盐酸利托君中有机溶剂残留量

建立盐酸利托君原料中有机溶剂残留量的分离测定方法.采用顶空气相色谱法,载气为氮气,FID检测器,色谱柱为HP-INNOWax毛细管柱,流速为2.0mL·min-1,外标法测定盐酸利托君中丙酮、乙酸乙酯、甲醇的残留量.3种有机溶剂完全分离,在所考察的浓度范围内具有良好的线性,r为0.9992～0.9997,平均回收率为95.7%～102.1%,精密度RSD均小于10%,检测限为0.21～2.02μg·mL-1.本方法快速、灵敏、准确,适用于盐酸利托君中有机溶剂残留量的测定.     

顶空气相色谱法测定阿莫西林钠中残留溶剂

目的：建立阿莫西林钠原料药中有机溶剂残留量的分离测定方法.方法：采用顶空气相色谱法,载气为氮气,FID检测器,色谱柱为HP-1毛细管柱,程序升温,外标法测定了阿莫西林钠中乙醇、异丙醇、二氯甲烷、二乙胺、三乙胺的残留量.结果：5种有机溶剂完全分离,在所考察的浓度范围内具有良好的线性关系,r为0.999 0～0.999 5,平均回收率为92.9%～105.7%,RSD均小于10%,最低检测限为0.004～0.05μg·ml-1.结论：方法快速、灵敏,适用于阿莫西林钠中有机溶剂残留量的测定.     

顶空气相色谱法测定左旋氟比洛芬有机溶剂残留量

建立了左旋氟比洛芬原料中几种有机溶剂残留量的分离测定方法.采用顶空气相色谱法,载气为氮气,FID检测器,色谱柱为HP-5毛细管柱,程序升温,以正丙醇为内标,测定左旋氟比洛芬中乙醇、乙酸乙酯和苯的残留量.几种有机溶剂完全分离,在所考察的浓度范围内具有良好的线性,r=0.9993～1.000,平均回收率为96.5%～102.4%,检测限为0.05～2.47ng·mL-1.本方法快速、灵敏、准确,适用于左旋氟比洛芬中有机溶剂残留量的测定.     

GC法检测氯法拉滨中有机溶剂的残留量

目的:建立以气相色谱法检测氯法拉滨原料药中7种有机溶剂残留量的方法。方法:毛细管柱为AT-1301;载气为氮气;检测器为火焰离子化检测器;柱温采取程序升温,初始温度40℃,以7℃.min-1升至80℃,再以20℃.min-1升至200℃,保持2min;进样口温度250℃;检测器温度280℃;分流直接进样。检测3批氯法拉滨原料药中甲醇、乙腈、二氯甲烷、叔丁醇、乙酸乙酯、正庚烷、乙酸的残留量。结果:各有机溶剂均能得到有效分离,在所考察的浓度范围内线性关系良好(r=0.99941～0.99993),平均回收率为96.5%～102.4%,RSD均小于4.0%,3批样品中7种有机溶剂残留量均符合《中国药典》要求。结论:本方法灵敏、准确、可靠,可用于氯法拉滨原料药中有机溶剂残留量的检测。     

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.

---

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.

     

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.     

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.     

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.