利用LC-MS/MS法快速鉴定盐酸头孢吡肟中的同分异构体杂质

目的建立应用LC-MS/MS技术快速鉴定盐酸头孢吡肟原料药中的同分异构体杂质的方法。方法以乙腈-10 mmol·L^-1乙酸铵(5∶95)为流动相经C₁₈柱分离,通过电喷雾串联质谱在线检测，获得相关的色谱和质谱信息。结果在所建立的条件下，盐酸头孢吡肟及其同分异构体杂质获得有效分离，主成分和其同分异构体杂质的保留时间分别为15.28 min和9.18 min，同时它们的二级质谱产物离子信息及其裂解方式呈现明显的差异。结论本法能快速、准确地分离鉴定盐酸头孢吡肟原料药中的同分异构体杂质，从而可以对其原料药进行质量控制。     

注射用头孢地嗪钠有关物质方法学研究

目的：建立注射用头孢地嗪有关物质检查方法。方法：采用高效液相色谱法,以Diamonsil-C18（250mm×4.6mm×5μm）为色谱柱;流动相：磷酸盐缓冲液（磷酸二氢钾0.87g与无水磷酸氢二钠0.22g加水溶解并稀释至1000ml）-乙腈（90：10）;检测波长：215nm。结果：有效的分离了注射用头孢地嗪钠中的有关物质,单个最大杂质峰面积不超过对照溶液主峰面积;各杂质峰面积的和不大于对照溶液主峰面积的1.5%。结论：此方法简便、快速,可用于注射用头孢地嗪钠的质量控制。     

2D-LC-HR-MS/MS法对头孢唑林钠中未知杂质的鉴定

摘要：目的 建立二维液相色谱-高分辨串联质谱(2D-LC-HR-MS/MS)法鉴定头孢唑林钠原料药中2个未知杂质的方法。方 法 采用二维液相-高分辨串联质谱法,一维色谱条件进行样品采集,确认一维色谱体系中目标峰的出峰位置,并进行分离, 二维液相脱盐后切进高分辨串联质谱进行分析,根据结果推断杂质结构及生成机理。结果 该方法有效解决了头孢唑林钠流动 相中含不挥发性盐的色谱体系不适用于色谱-质谱快速鉴定杂质的难题,并对2个未知杂质进行有效鉴定。结论 该方法可以简 单、快速地对头孢唑林钠中未知杂质进行定性     

LC-MS/MS法分析和鉴定抗肿瘤药MTC-220原料药中的杂质

目的:分析和鉴定抗肿瘤新药MTC-220中的杂质结构。方法:采用液相色谱-质谱(LC-MS/MS)法,根据降解反应机制设计合理的加速破坏条件,制备杂质含量较高的受试样品;以10mmol·L-1乙酸铵-乙腈-甲醇为流动相,采用C18柱分离和电喷雾串联质谱正离子检测模式,对MTC-220及紫外光照和碱破坏样品进行LC-MS/MS测定,推导MTC-220的降解途径,鉴定杂质结构。结果:MTC-220原料药中检测到3个杂质,经鉴定分别为MTC-220异构体、紫杉醇和反应副产物。结论:对MTC-220中的3个杂质成功地进行了结构鉴定。     

RRLC-QTOF鉴定拉科酰胺的未知杂质

目的通过快速液相-四极杆飞行时间串联质谱（RRLC-QTOF）法分离、鉴定拉科酰胺粗品中4个未知杂质。方法采用美国AgilentRRLC快速液相色谱系统和6530型四极杆-飞行时间串联质谱仪,色谱柱为XDB-C18（150mm×4．6mm,5μm）,流动相为醋酸铵．水溶液（甲酸调节pH至4．5）和乙腈,梯度洗脱,流速为1．0mL·min^-1,采用柱后分流,其中质谱仪进样流速为0．3mL·min^-1。结果结合高分辨质量数和二级质谱碎片推测得到了拉科酰胺粗品中4个可能的杂质结构。结论本研究为拉科酰胺的质量研究提供参考。     

地佐辛注射液有关物质的色谱-质谱结构鉴定

目的：采用色谱-质谱联用技术鉴定地佐辛注射液中的有关物质。方法：采用Agilent Eclipse Plus C₁₈(150 mm×4.6 mm,5μm)色谱柱,以甲醇-10 mmol·L^-1甲酸铵缓冲溶液(甲酸调节pH至2.7)为流动相梯度洗脱,对地佐辛注射液有关物质进行分离,电喷雾正离子化-四极杆-飞行时间串联高分辨质谱(ESI-Q-TOF/MS)测定各有关物质母离子及其子离子的准确质量和元素组成,通过光谱解析鉴定其结构。结果：在所建立的分析条件下,地佐辛及其有关物质分离良好,检测并鉴定出地佐辛注射液及其强制降解试验样品中20个含量大于0.1%的有关物质,其中2个为已知杂质,其他杂质均未见报道。结论：色谱-质谱联用技术能有效地分离鉴定地佐辛注射液中的有关物质,为其质量控制提供参考依据。     

双苯氟嗪中杂质的结构分析

目的:采用高效液相色谱-串联质谱(HPLC-MS/MS)和高效液相色谱-二极管阵列检测(HPLC-PDA)法对双苯氟嗪中的杂质进行结构分析。方法:采用C18柱,甲酸铵溶液(用甲酸调节pH至3.2)-甲醇为流动相,线性梯度洗脱,流速0.5 mL.min-1,柱温45℃,MS/MS和PDA分别检测。结果:双苯氟嗪中的主要杂质有效分离,通过解析获取的质谱和紫外信息,结合原料合成工艺,对其中3个未知杂质的结构进行了推断。结论:本实验分离鉴别了双苯氟嗪中的主要杂质,为双苯氟嗪的质量控制和工艺优化提供了参考。     

头孢地尼原料及制剂的聚合物杂质分析

目的 建立头孢地尼原料及制剂聚合物杂质的分析方法。方法 分别采用0.1mol/L磷酸盐溶液和氯仿-三乙胺为溶剂,制备头孢地尼降解溶液;采用高效凝胶色谱法(HPSEC, TSK G2000 SWxl)和柱切换-LC/MSn法对头孢地尼降解溶液的弱保留值杂质进行分离和结构鉴定,并评估高效凝胶色谱法分析聚合物杂质的专属性;采用Diamonsil, C18型色谱柱,以0.25%四甲基氢氧化铵溶液(pH5.5)-甲醇-乙腈为流动相进行梯度洗脱,建立头孢地尼聚合物的RP-HPLC分析方法,采用二维色谱法和柱切换-LC/MSn法对其专属性进行分析,并进行方法学验证。结果 在头孢地尼降解物中鉴定出头孢地尼二聚体及其异构体,以及若干小分子杂质;高效凝胶色谱法分离头孢地尼聚合物杂质时,小分子杂质与聚合物杂质共出峰,方法专属性与定量准确性差;RP-HPLC法分析头孢地尼聚合物杂质时,能够检出头孢地尼二聚体及其异构体,头孢地尼三聚体,专属性好。结论 高效凝胶色谱法不能对头孢地尼的聚合物杂质进行有效质控,建立的反相色谱法分析头孢地尼聚合物杂质的专属性良好,可将头孢地尼降解溶液可作为聚合物杂质系统适用性溶液。     

2D-LC-IT-TOF-MS/MS联用Cef-SEC法测定注射用盐酸头孢吡肟中的多聚体杂质

目的:建立高效分子排阻色谱法(Cef-SEC)测定注射用盐酸头孢吡肟中的多聚体杂质,并应用在线脱盐-高效液相色谱-离子阱-飞行时间质谱联用技术(2D-LC-IT-TOF-MS/MS)对检出的四个杂质进行鉴定.方法:色谱柱:SRT-Cef-SEC(300 mm×7.8 mm,5μm);流动相:5 mmol·L-1磷酸盐缓...     

HPLC法测定丙二醇头孢曲嗪的有关物质

目的建立高效液相色谱法测定丙二醇头孢曲嗪的有关物质。方法采用Diamonsil C18色谱柱(250×4.6mm,5μm),以0.272%磷酸二氢钾溶液-乙腈(95∶5)为流动相,流速2.0mL.min-1,检测波长270nm。结果丙二醇头孢曲嗪主峰能与相邻杂质峰较好分离。结论本法简便,准确,可对丙二醇头孢曲嗪的有关物质进行控制。     

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.     

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.     

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.     

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.