UPLC-Q-TOF-MS快速测定减肥类保健食品中非法添加的双氯芬酸

目的 建立超高效液相色谱四极杆飞行时间串联质谱法测定减肥类保健食品中非法添加双氯芬酸化学药物的检测方法。方法 采用 phenomenex C₁₈色谱柱分离,以0.02 mol·L^-1醋酸铵溶液和乙腈梯度洗脱,采用TOF,MS/MS扫描模式检测。结果 经对照品确认,样品中检测出双氯芬酸,该化合物在减肥类保健食品中尚未见报道。结论 本方法可以用于快速鉴定减肥类保健食品中非法添加双氯芬酸物质的检测。     

保健食品中非法添加西地那非衍生物的确证

目的：对在保健食品中发现的一种非法添加的西地那非衍生物进行确证。方法：采用高效液相色谱-二极管阵列检测器（HPLC-DAD）技术在日常检测保健食品非法添加时发现一种新型西地那非衍生物。经制备液相法分离纯化得到该化合物,采用高效液相色谱-二级质谱联用（LC-MS/MS）技术获得该化合物准分子离子和碎片离子,并进一步通过核磁共振氢谱确认,结合文献分析,最终确证该化合物。结果：该化合物分子式C₂₃H₃₀N₆O₃,分子量438,结构为去甲基卡波地那非。结论：去甲基卡波地那非在国内未被报道,是一种新型PDE-5抑制剂。     

LC-MS检测金锁固精丸中非法添加的枸橼酸西地那非

目的 采用液质联用技术检测金锁固精丸中非法添加的枸橼酸西地那非。方法 选用C₁₈色谱柱(2.1 mm×100 mm,5 µm),以乙腈-0.01 mol·L^-1乙酸铵溶液梯度洗脱,对此制剂的提取液进行液质联用分析,通过与对照品的色谱和质谱行为比较,检测此制剂中枸橼酸西地那非成分。结果 在该金锁固精丸中检出枸橼酸西地那非。结论 本方法简便、灵敏、准确,专属性强,可分析检测此制剂中的枸橼酸西地那非。     

基于网络搜索快速鉴定抗风湿类中成药和保健食品中非法添加的非那西丁及小檗碱

目的 鉴定抗风湿类中成药和保健食品中非法添加的2个未知成分。方法 采用高效液相色谱-二极管阵列检测器联用（HPLC-DAD）技术进行抗风湿类中成药和保健食品非法添加筛查时发现2个可疑色谱峰,采用UPLC-MS/MS技术获得其准分子离子和二级质谱图,然后通过网络搜索分析初步确定可疑成分,最后与对照品比较检测,最终确定2个非法添加化合物的结构。结果 在抗风湿类保健食品中检出盐酸小檗碱,中成药中检出非那西丁。结论 这2个化合物不在现有抗风湿类中成药和保健食品检验标准13种目标化合物范围内,容易逃脱标准监管范围。     

液质联用法检查中成药及保健食品非法添加的17种辅助改善记忆类药物

摘 要 目的：建立准确、灵敏的LC MS/MS方法甄别中药制剂及保健食品中可能非法添加的17种辅助改善记忆类药物。方法: 采用液相色谱-串联质谱法（LC-MS/MS）,以Eclipse XDBC₁₈（100 mm×3.0 mm,1.8 μm）为分析柱,以电喷雾电离（ESI）、多反应监测（MRM）扫描方式,对中药制剂及保健食品中非法添加的17种化学成分进行快速定性定量分析。结果: 建立了快速分离检测17种非法添加成分的测定方法,检测限低于10 ng·mL^-1。结论:该方法专属性强、灵敏度高,可用于辅助改善记忆类中药制剂及保健食品中非法添加化学成分的定性和定量分析。     

降糖保健食品和中成药中12种化学药的液相快速筛查

目的 建立降糖保健食品和中成药中12种化学药的液相快速筛查方法。方法 采用HPLC-DAD,色谱条件：Agilent Extend C₁₈色谱柱(4.6 mm×250 mm,5 μm),以0.014%三氟乙酸水溶液(pH 2.7±0.05)、0.01 mol·L^-1庚烷磺酸钠溶液、乙腈为三元梯度洗脱流动相,柱温：30 ℃,流速：1.0 mL·min^-1,检测波长：220 nm。结果 12种化学降糖药实现了同时分离与专属性鉴别;利用本法从28种39批样品中检出7种12批非法添加化学药品。结论 本法可用于降糖类保健食品及中成药中非法添加12种化学降糖药的快速筛查。     

中成药中非法添加10种喹诺酮类药物的LC-MS/MS检测方法研究

摘 要 目的： 建立检查中成药和保健食品中非法添加喹诺酮类抗菌药物的专属性方法。方法: 采用液相色谱 三重四极杆质谱联用法（LC MS/MS）同时检测中成药和保健食品中非法添加的吡哌酸、诺氟沙星、环丙沙星、洛美沙星、依诺沙星、氟罗沙星、培氟沙星、司帕沙星、加替沙星、氧氟沙星10种成分,进行定性和定量分析,并进行了方法学验证。结果: 本分析方法条件下10种常被用于非法添加的喹诺酮类药物在色谱柱中得到了较好的分离,再配合二级质谱图进行定性,利用多反应监测模式的峰面积进行定量计算,专属性强,精密度良好,回收率和线性关系满足筛查需求。结论:该方法简便、准确,可以应用于中成药和保健食品中非法添加喹诺酮类化学成分的实验室筛查。     

中成药和保健食品中18种非法添加降压药物的HPLC QTOF/MS定性检测

摘 要 目的：建立降压类中成药和保健食品中非法添加18种降压药物的液相色谱串联四级杆飞行时间质谱（HPLC-QTOF/MS）快速定性检测方法。方法: 采用Agilent Eclipse plusC₁₈(50 mm×2.1 mm,1.8 μm)色谱柱进行分离,以0.5%甲酸水-乙腈为流动相梯度洗脱,流速为0.2 ml·min^-1,离子源为ESI源,正离子检测模式,对降压类中成药及保健品中非法添加的该18种化学药物进行定性检测。结果: 18种化学药物的检出限分别为0.2～2.5 ng·mL^-1,12批供试品中有1批检测到添加了利血平。结论:该方法专属性强、灵敏度高,适用于降压类中成药及保健品中非法添加该18种化学药物的定性分析。     

保健食品中新型二硫代卡地那非类似物的分析鉴定

目的 鉴定保健食品中非法添加的一个未知结构的二硫代卡地那非类似物。方法 采用高效液相色谱-二极管阵列检测器联用（HPLC-DAD）技术进行补肾壮阳类保健食品非法添加筛查时发现一个未知结构的二硫代卡地那非类似物,经过正相硅胶薄层色谱分离纯化得到目标化合物后,用超高效液相色谱-二级质谱联用（UPLC-MS/MS）技术获得其准分子离子和二级质谱图,用核磁共振得到碳谱和氢谱数据,结合文献分析,最终鉴定该化合物的结构。结果 在保健食品中发现了一个新型二硫代卡地那非类似物,结构为3,5-二甲基哌嗪基二硫代去甲卡地那非。结论 该化合物不在现有补肾壮阳类中成药检验标准的13种目标化合物范围内,是一种新的非法添加化学物质。     

液质联用法检测镇静安神类中药制剂及保健品中非法掺入的化学品

目的: 建立检测镇静安神类中药制剂和保健品中非法掺入化学品的液质联用方法,并对10批市售样品进行检测。方法: 采用液相色谱-离子阱质谱法,选用C₁₈柱,分别以甲醇-乙腈-0.5%甲酸(15:25:60)和甲醇-水(60:40)为流动相,对样品的提取液进行分析。结果: 在10批受试制剂中,1批被检测出非法掺有地西泮。结论: 该法选择性强,灵敏度高,可以用于分析检测中药制剂及保健品中是否掺入相应化学品。     

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.     

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.     

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.