RP—HPLC法测定益列康宁片中美帕曲星的含量

目的:采用RP-HPLC法测定益列康宁片中美帕曲星的含量。方法:采用LiChroCART RP-18不锈钢柱,以乙腈和0.005 mol·L~(-1)乙二胺四乙酸二钠混合溶剂作流动相,梯度洗脱,流速1.0 mL·min~(-1),检测波长378 nm。结果:美帕曲星在100～300μg·mL~(-1)浓度范围内呈现良好的线性关系(r=0.999 9),平均回收率为99.4％～100.4％,RSD<1.3％(n=3)。日内RSD为0.5％～0.9％(n=5),日间RSD为1.2％～1.7％(n=5)。结论:本法简便,精密度高,重现性好,结果准确可靠。     

RP—HPLC法测定大鼠血清中蟾蜍灵浓度

目的:建立反相高效液相色谱法测定大鼠血清中蟾蜍灵浓度。方法:血清样品用乙醚-乙酸乙酯(5:1)提取两次,40℃水浴氮气吹干,残留物用甲醇溶解后进样。色谱柱为Shim-pack VP-ODS柱(4.6 mm×150mm,5 μm),流动相为甲醇-水(70:30),流速1.0 mL·min～1,紫外检测波长298 nm,柱箱温度30℃。内标物为华蟾酥毒基。结果:本法最低检测浓度为0.05μg·mL～1,线性范围为0.1-1.6μg·mL-1,r=0.9977。日内精密度RSD小于4％,日间RSD小于10％,蟾蜍灵的萃取回收率为84.0％。结论:本法快速、准确、灵敏,可用于蟾蜍灵的体内药物动力学研究。     

高效液相色谱法测定莫达非尼及其胶囊剂含量

目的:测定莫达非尼原料药及其胶囊剂的含量。方法:采用高效液相色谱法。色谱柱为Phenomenex ODS(150mm×4.6mm,5μm),柱温30℃,流动相为甲醇-50mmoL·L~(-1)甲酸(50:50,pH=2.5),流速1.0mL·min~(-1),UV检测波长225nm。结果:莫达非尼浓度在1.0～20μg·mL~(-1)范围标准曲线线性良好,最低检测浓度0.5μg·L~(-1),日内RSD为1.8％(n=5),日间RSD为2.0％(n=5),加样回收率98.0％～99.6％(n=3)。结论:本法简便快速,准确可靠,可用于莫达非尼及其胶囊剂含量测定等相关研究。     

HPLC法同时测定人血浆中舒必利、氯氮平、氯丙嗪浓度

目的:建立同时测定人血浆中舒必利、氯氮平、氯丙嗪药物浓度的高效液相色谱方法。方法:血浆样品用乙酸乙酯萃取,氮气吹干;残留物用甲醇溶解后进样。色谱柱为C_(18)柱(250 mm×4.6mm),流动相为甲醇-水(80:20,含0.5％三乙胺和0.05％冰醋酸,pH=7.6～7.8),流速:1.0mL·min~(-1),柱温:35T,紫外检测波长:250nm。结果:本法可同时测定血浆中3种药物浓度。舒必利在0.2～1.0μg·mL~(-1)、氯氮平在0.05～1.0μg·mL~(-1)、氯丙嗪在0.01～0.16μg·mL~(-1)范围内,峰面积与其浓度呈良好的线性关系;日内RSD分别为2.9％～3.9％,3.1％～4.1％,3.0％～4.3％;日间RSD分别为3.9％～4.8％,3.8％～5.1％,4.3％～5.3％(n=4)。结论:方法简便、快速、准确,适用于舒必利、氯氮平、氯丙嗪3种药物临床血药浓度的同时检测。     

RP-HPLC法测定人体血浆中吉西他滨的浓度

目的:建立一种测定人体血浆中吉西他滨血药浓度的高效液相色谱方法。方法:取血浆样品1 mL,加内标100μL(含氟脲苷0.8μg·mL-1),混匀,加甲醇-乙腈(1:9)3 mL混匀,放置5 min,离心(3500 r·min-1,10 min),取上清液于60℃水浴放置,氮气吹干,残渣用0.5 mL流动相溶解,离心(15000 r·min～1,10 min),取上清液,进样50μL。色谱柱:Lichrospher 5-C18(4.6 mm×250 mm,5 μm),流动相:40 mmol·L-1醋酸铵缓冲液(用醋酸调节pH=5.5)-乙腈(97.5:2.5),流速:0.8 mL·min～1,检测波长:268 nm,柱温:25℃。结果:本方法线性范围0.20—10.0μg·mL～1,r=0.9999,方法检测限为0.10μg·mL-1(S/N>4),定量限为(0.21±0.02)μg·mL-1(S/N>10);方法回收率为100.1％-106.6％(n=21),日内RSD为2.3％-4.0％(n=21),日间RSD为3.2％-5.2％(n=21)。结论:本方法灵敏度高,操作简便、准确,可用于人体血浆中吉西他滨浓度的测定及药动学研究。     

反相高效液相色谱法测定人血浆中非诺贝特活性代谢物非诺贝酸

目的:建立以高效液相色谱法测定人血浆中非诺贝特活性代谢物非诺贝酸的方法。方法:血浆样品酸化后用乙醚萃取;色谱柱为Shim-pack VP-ODS(150mm×4．6mm),柱温为40℃,流动相为甲醇-水-10％磷酸(80:19:1),流速为1．0mL·min-1,检测波长为290nm,外标法峰高定量。结果:非诺贝酸的保留时间约为5．6min,定量线性范围为0．25～18．75μg·mL-1,绝对回收率>85％(n=5),方法回收率为96％～103％(n=5),日内、日间RSD<10％(n=5)。结论:本方法简便快速、定量准确,适用于非诺贝特临床药动学研究。     

反相高效液相色谱法测定发酵液中梅岭霉素

目的:建立了发酵液中梅岭霉素的定量测定方法。方法:反相高效液相色谱法,Hypersil-C_(18)柱(4 mm×125mm,5μm),流动相为乙腈-水(78:22),流速1.2mL·min~(-1),检测波长238 nm,室温测定。结果:在1O.2～163.2μg·mL~(-1)范围内梅岭霉素浓度与峰面积呈良好线性关系,r=0.999 7,回归方程为Y=25.44X+2.72。样品的日间 RSD≤1.8％,高中低浓度样品的日内RSD≤2.5％(n=8)。平均回收率为96.9％(n=8,RSD<3.0％)。结论:本方法快速、准确、简便、稳定,为定量分析提供了可靠的依据。     

反相高效液相色谱法测定氨氯地平血药浓度

目的 　建立反相高效液相色谱法 ( HPLC)测定人血浆中氨氯地平浓度。 方法 　血浆样品用重蒸馏乙醚提取 ,以达克罗宁为内标 ;甲醇 -0 .0 3 mol· L- 1磷酸二氢钾缓冲液 ( 72∶ 2 8)为流动相 ,流速 1.0 ml·min- 1 ;检测波长 2 3 8nm;柱温 :室温。 结果 　本法在 1.0～ 12 .0 ng·m L- 1范围内线性关系良好 ,r=0 .9980。日内 RSD为 3 .7%～ 6.7% ( n=5 ) ,日间 RSD为 6.0 %～ 7.1% ( n=15 ) ;回收率 89.0 %～ 10 1.7% ;血清最低检测浓度为 0 .15 ng·m L- 1 ( S/N=2 )。 结论 　本法灵敏、准确、快速 ,为该药物的临床血药浓度监测和药代动力学研究提供依据。     

HPLC法测定尼莫地平纳米脂质体药物含量及包封率

目的:建立尼莫地平脂质体药物含量测定及包封率测定的RP-HPLC法。方法:采用Hypersil ODS柱(250mm×4.6mm,5μm);流动相:甲醇-水-四氢呋喃(40:30:30);柱温:30℃;流速:1mL·min~(-1) ;紫外检测波长:237nm。采用透析法分离尼莫地平脂质体中的游离药物。结果:在本色谱条件下尼莫地平与辅料及溶剂峰分离良好,尼莫地平在0.2～45μg·mL~(-1)范围内线性关系良好(r=0.999 9,n=5),回收率在99.90％～102.0％之间,日内RSD及日间RSD均小于3％(n=5)。结论:说明该方法准确可靠、简单快速,可用于尼莫地平纳米脂质体含量及包封率的测定。     

NP-HPLC法监测人血浆中4种苯并二氮(?)药物浓度

目的:建立监测人血浆中咪达唑仑、三唑仑、艾司唑仑和阿普唑仑药物浓度的正相高效液相色谱方法。方法:血浆样品用乙醚萃取,55℃水浴中氮气吹干;残留物用乙醇溶解后进样。色谱柱为Shim-pack CLC-CN 柱(150 mm×6.0 mm,5μm),流动相为正己烷-无水乙醇-甲醇(76:18:6),流速为1.10 mL·min-1,柱温为:40℃,紫外检测波长为230 nm。结果:本方法可用于同时测定血浆中4种药物的浓度。咪达唑仑、三唑仑、艾司唑仑和阿普唑仑在0.050-20.0μg·mL-1范围内线性关系良好(r≥0.9996),准确度分别为98.9％,99.8％,101.8％及100.5％(n=6)。日内和日间RSD均不大于5.1％(n=6)。结论:本方法灵敏、特异性强、准确、简便易行,适用于咪达唑仑、三唑仑、艾司唑仑和阿普唑仑4种药物血浓度的临床监测。     

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.

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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.