反相高效液相色潽法同时测定人血浆齐拉西酮与阿立哌唑浓度

目的建立同时测定人血浆中齐拉西酮与阿立哌唑浓度的反相高效液相色谱法。方法以DiamonsilTM C18反相柱（150 mm×4.6 mm,5 μm）为色谱柱,流动相为0.03 mol•L 1醋酸铵 甲醇（14：86）;流速：0.8 mL•min 1;柱温：40 ℃; 检测波长： 254 nm。以乙酸乙酯与二氯甲烷（80：20）为提取剂。结果齐拉西酮在20.0～640.0 ng•mL 1、阿立哌唑在25.0～1 000.0 ng•mL 1浓度范围内,峰面积与其浓度呈良好线性关系;齐拉西酮、阿立哌唑的高、中、低浓度相对平均回收率分别为96.95%,97.71%,100.21%和97.87%,98.36%,101.82%,提取回收率分别为71.42%,74.33%,78.26%和72.67%,76.51%,79.32%;日内、日间RSD均＜9%（n=5）。分析方法的检测限10.0 ng•mL 1;齐拉西酮曲线方程： Y=61.717X＋2.16,r = 0.998 9（n=7）;阿立哌唑曲线方程： Y=87.946X＋1.37,r = 0.999 1（n=7）。结论该方法灵敏、准确、简单、快速,可用于临床齐拉西酮与阿立哌唑的血浆浓度监测和药动学研究。     

反相高效液相色谱法检测肝灌流液中更昔洛韦

（1. ［摘要］目的建立P-糖蛋白底物更昔洛韦在肝灌流液中浓度的测定方法。方法将SD雄性大鼠施行肝脏灌流手术，收集肝灌流液。采用反相高效液相色谱法，应用外标法测定更昔洛韦在SD大鼠中的药物浓度。结果在所建立的方法学下，更昔洛韦的保留时间为6.68 min。 标准曲线为Y＝0.052X－0.172(r＝0.999 9)，在50 ～2 500 ng&;#8226; mL 1肝灌流液浓度范围内呈良好的线性关系，最低定量限为50 ng&;#8226; mL 1;在100，1 000，2 000 ng&;#8226; mL 1低、中、高三个浓度下的绝对回收率为90.57%～94.78%，方法回收率为98.68%～105.59% ，日内精密度＜11.00%，日间精密度＜15.30%(n＝5)。结论该方法快速、准确、简便，能够满足更昔洛韦药动学研究要求。     

当归养血丸中阿魏酸的含量测定

目的建立当归养血丸中阿魏酸的反相高效液相色谱（RP HPLC）含量测定方法.方法采用RP HPLC法,色谱柱：ZORBAX Eclipse XDB C18（4.6 mm×150 mm,5 μm）,流动相：乙腈：0.085 %（V/V）磷酸水溶液＝ 14：86,检测波长：314 nm,流速：1.0 mL&;#8226;min 1.结果阿魏酸在1.5～15.0 μg&;#8226;mL 1范围内呈良好的线性关系（r＝0.999 6）,平均回收率为97.2 %（RSD ＝2.7%）.结论该方法简便、准确,可用于控制当归养血丸的质量.     

高效液相色谱法测定复方丙酸倍氯米松乳膏中丙酸倍氯米松和氯霉素的含量

［摘要］目的建立测定复方丙酸倍氯米松乳膏中丙酸倍氯米松和氯霉素含量的高效液相色谱（HPLC）法。方法采用Hypersil ODS2色谱柱（4.6 mm×250 mm,5 μm）,流速：1.0 mL&;#8226;min 1,柱温：24 ℃。丙酸倍氯米松的检测波长为240 nm,流动相为甲醇 水（85：15）;氯霉素的检测波长为278 nm,流动相为甲醇 水（65：35）。结果丙酸倍氯米松的线性方程为A＝3 600.6C＋1 172（r＝0.999 8）,在2.5～25.0 μg&;#8226;mL 1范围内呈良好的线性关系,低、中、高浓度平均回收率分别为98.68%,98.75%,101.77%,重复性的RSD为0.82%;中间精密度的RSD为1.75%。氯霉素的线性方程为A＝3 709.9 C＋5 464.7（r＝0.999 9）,在25.0～240.0 μg&;#8226;mL 1范围内呈良好的线性关系,平均回收率分别为99.80%,100.08%,100.93%,重复性的RSD为0.62%,中间精密度的RSD为1.24%。结论所建立的方法准确、可靠,可用于复方丙酸倍氯米松乳膏的质量控制。     

高效液相色谱法同时测定人血浆氯氮平与奋乃静浓度

［摘要］目的建立同时测定人血浆中氯氮平、奋乃静浓度的高效液相色谱法。方法以DiamonsilTM C18反相柱（150 mm×4.6 mm, 5 μm）为色谱柱,流动相为0.03 mol•L 1醋酸铵 甲醇（27：73）;流速：0.8 mL•min 1;柱温：40 ℃;检测波长：254 nm。以乙酸乙酯与二氯甲烷（80：20）为提取剂。结果氯氮平高、中、低3种浓度平均回收率分别为98.28%,97.63%,101.31%;奋乃静高、中、低3种浓度平均回收率分别为97.26%,98.65%,100.42%。日内、日间差RSD均＜7%（n＝5）;分析方法的检测限为5.0 ng•mL 1;两者在10.0～1 000.0 ng•mL 1浓度范围内线性良好。氯氮平曲线方程：Y＝1.692X＋4.390,r＝0.999 4（n＝10）;奋乃静曲线方程：Y＝0.575X－2.370,r＝0.999 2（n＝10）。结论该方法灵敏、准确、简单、快速,可用于临床血药浓度监测和药动学研究。     

高效液相色谱-蒸发光散射检测法检测天然牛黄与酶促牛黄中胆固醇含量

［摘要］目的建立高效液相色谱 蒸发光散射检测（HPLC ELSD）法,测定并比较天然牛黄与酶促牛黄中胆固醇的含量。方法色谱柱为Diamonsil C18柱（250 mm×4.6 mm,5 μm）;以乙腈 异丙醇（1：1）为流动相,流速1.0 mL&;#8226;min 1;漂移管温度67.5 ℃,气体流速1.7 L&;#8226;min 1。结果胆固醇浓度在4.0～20.0 μg&;#8226;mL 1范围,浓度对数（logC）与峰面积对数（logA）呈良好的线性关系logA＝1.541 2logC－2.525 （r＝0.999 2）;低、中、高浓度平均回收率分别为98.41%,100.04%,96.46%,RSD分别为0.63%,1.67%,1.03%。结论该法简便、准确,专属强,可用于牛黄、牛黄替代品及其制剂的质量控制。     

高效液相色谱法测定人血浆中氯氮平浓度

目的 建立测定人血浆中氯氮平浓度的高效液相色谱法. 方法 以DiamonsilTM C18反相柱（150 mm×4.6 mm,5 μm）为色谱柱,流动相为0.03 mol•L^-1醋酸铵 甲醇（25：75）;流速0.8 mL•min^-1,柱温40 ℃,检测波长 254 nm. 以醋酸乙酯与二氯甲烷（80：20）为提取剂. 结果 氯氮平的高、中、低（1 000.0,400.0,10.0 ng•mL^-1）3种浓度平均回收率分别为98.28%,97.63%,101.41%,日内、日间精密度RSD均＜7%（n＝5）;分析方法 的检测限为5.0 ng•mL^-1;线性范围为10.0～1 000.0 ng•mL-1. 曲线方程：C＝25.69F＋3.47,r＝0.999 7（n＝10）. 结论 该方法 灵敏、准确、简单、快速,可用于临床血药浓度监测和药动学研究.     

人血浆中盐酸氨溴索的HPLC测定及其在药动学研究中的应用

［摘要］　目的：建立人血浆中盐酸氨溴索浓度HPFC测定法。方法：采用液-液萃取高效液相色谱紫外检测法，以盐酸尼卡地平为内标，色谱柱为Diamonsil C18柱（150 mm×4.6 mm，5 μm），流动相为甲醇-乙腈-0.01 mol•L-1磷酸盐缓冲液（45∶27∶28），流速为1 mL•min-1，检测波长245 nm。结果：盐酸氨溴索血浆浓度测定方法线性范围为10~480 ng•mL-1，r=0.999 9，定量下限为10 ng•mL-1，方法回收率＞94%。日内和日间RSD＜5%。结论：本试验所建立起来的人血浆中盐酸氨溴索浓度测定法灵敏、准确，可靠，适用于盐酸氨溴索的人体药动学研究。     

高效液相色谱-串联质谱法测定大鼠血浆紫檀芪浓度简

摘要 目的 建立高效液相色谱 串联质谱法（LC MS/MS）测定大鼠血浆紫檀芪浓度。方法血浆样品经乙醚液液萃取处理。分析柱为Thermo Hypsil Gold色谱柱（2.1 mm×50 mm,5.0 μm）,保护柱为Thermo C18 柱（4 mm×3.0 mm,10.0 μm）,以乙腈 水（含1 mmol•L－1 甲酸铵）为流动相梯度洗脱,流速为0.3 mL•min－1,进样量10 μL,内标为白藜芦醇,采用电喷雾离子源（ESI）,以多反应监测（MRM）模式检测。用于定量紫檀芪和内标的MRM扫描离子通道分别为m/z 255.1→240.2,227.1→143.0。每个样品的分析时间为5 min。结果紫檀芪和内标的保留时间分别为2.07,1.90 min。血浆中内源性物质对测定无干扰,紫檀芪的线性范围为1～100 ng•mL－1,日内、日间精密度（RSD）均＜15 %;血浆低、中、高3种浓度（3,50,80 ng•mL－1）紫檀芪苷的准确度分别为103.10%,98.12%和93.23%;血浆低、中、高3 种浓度（3,50,80 ng•mL－1）紫檀芪的萃取回收率分别为78.6%,80.3%和83.2%;检测方法不受基质效应影响。结论该方法灵敏、准确、快速,测定结果可靠,可用于紫檀芪的药动学研究。     

测定注射用头孢哌酮钠含量色谱条件的改进

目的改进注射用头孢哌酮钠含量测定方法中色谱条件.方法色谱柱：DiamonsilTM（钻石）C18（4.6 mm×200 mm,5 μm）;检测波长：254 nm; 流动相：三乙胺醋酸溶液（取三乙胺14 mL与冰醋酸5.7 mL ,加水稀释至100 mL,摇匀 ） 醋酸 乙腈 水（1.2：2.8：250：820） ;柱温：35 ℃;流速：0.9 mL&;#8226;min 1;进样量：10 μL.结果头孢哌酮的线性范围为100.8 ～2 016.0 μg&;#8226;mL 1（r＝0.999 9）,平均回收率为99.3%,RSD为0.3%.结论该方法快速、简便易行、结果准确.     

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.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

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.     

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.