双嘧达莫2种定量分析方法的比较

目的:探讨高氯酸非水滴定法和高效液相色谱(HPLC)法测定双嘧达莫原料药含量的可行性。方法:非水滴定法采用电位法指示终点,并考察不同溶剂对滴定的影响;HPLC法中,色谱柱为C18,流动相为乙腈-20mmol·L-1磷酸二氢钾(含1.0%三乙胺,磷酸调pH至4.0)=35∶65;并与《中国药典》规定的溴酸钾滴定法进行比较。结果:非水滴定法、HPLC法和溴酸钾滴定法的含量分别为101.36%、101.11%、100.56%。结论:高氯酸非水滴定法和HPLC法均可用于双嘧达莫原料药的含量测定,且高氯酸非水滴定法操作更简便、快捷。     

碳糊电极阳极伏安法测定秋水仙碱

在0.05mol·L^-1H₂SO₄介质中,用碳糊电极(石墨粉:液体石蜡油=1.5∶1)阳极扫描伏安法测定秋水仙碱,检测限1×10^-7mol·L^-1,检测线性范围4.0×10^-7～1×10^-3mol·L^-1,氧化时出现两个氧化峰,峰电位分别为1.07V和1.33VvsSCE,峰电位随pH值升高而正移。对原料和片剂进行了测定,均获得满意的结果。     

非水滴定法测定奈拉滨原料药的含量

目的 建立奈拉滨原料药的含量测定方法.方法 以0.1 mol/L的高氯酸溶液为滴定液,采用非水滴定法测定,并比较了不同溶剂和不同指标剂对测定结果的影响.结果 以冰醋酸为溶剂,照电位滴定法滴定,终点明显,方法可行.连续测定5次,平均含量为99.8%(RSD=0.22%),测得结果与液相色谱法结果基本一致.结论该方法操作简便、精密度高,可作为奈拉滨原料药含量测定的方法.     

马蔺子素的单扫描示波极谱法测定

目的建立测定马蔺子素的极谱法。方法单扫描示波极谱法。结果在8.0×10^-3 mol·L^-1 Na₂B₄O₇-1.6×10^-2 mol·L^-1 KH₂PO₄ (pH 7.7)支持电解质中,马蔺子素有一灵敏的极谱还原波,其峰电位E_p=-1.23 V(vs SCE),二阶导数峰电流i_p″与马蔺子素浓度为1.5×10^-7～5.2×10^-6 mol·L^-1呈良好线性关系(γ=0.9992,N=9),检出限为6.0×10^-8 mol·L^-1。13次测量2.0×10^-6 mol·L^-1马蔺子素还原波二阶导数峰峰电流,相对标准偏差RSD为0.87%。结论该方法灵敏、简便、快速,可用于原料药及胶囊中马蔺子素含量的测定。     

妥洛特罗透皮贴剂的释放度测定及不同测定方法结果比较

目的 建立妥洛特罗透皮贴剂的释放度测定方法,并对不同装置测定的释放曲线进行比较。方法 采用中国药典2015年版收载的2种透皮贴剂释放度测定新方法,即桨碟法和转筒法,规定时间点取样后采用HPLC测定,色谱柱为Agilent C₁₈（250 mm×4.6 mm,5 μm）,流动相为乙腈-0.02 mol·L^-1磷酸盐缓冲液（pH 3.0）（32：68）,流速为1.0 mL·min^-1,柱温为35℃,检测波长为215 nm。分别考察妥洛特罗透皮贴剂在500 mL水中24 h的释放曲线,并对2种方法的释放曲线进行拟合,比较二者的相似性。结果 妥洛特罗在0.103~4.135 μg·mL^-1内线性关系良好（r=0.999 9）,回收率为99.8%（n=9）,样品溶液在24 h内稳定。将2种方法测定的释放度结果经Weibull方程拟合后得到的参数进行方差分析,2组数据间无显著性差异。结论 中国药典2015年版透皮贴剂释放度测定桨碟法（方法2）和转筒法均可用于妥洛特罗透皮贴剂的释放度测定,两者的测定结果不存在差异。     

氟罗沙星原料药中的杂质检查

目的　采用反相高效液相色谱法进行氟罗沙星原料药的杂质限量检查。方法　以乙腈-三乙胺及磷酸混合液 (15∶85)为流动相 ,Phenomenex C₈柱 (2.50mm×4.6mm ,5 μm)为固定相 ,流速为1.0ml·min^-1,检测波长为 286nm。结果　通过自身对照法用面积归一化法计算的氟罗沙星原料药中杂质含量均未超过 1%。结论　方法简单、灵敏度高 ,可用于氟罗沙星原料药的杂质含量测定。     

帕拉米韦原料含量测定方法比较研究

目的：建立并比较高氯酸非水滴定法和高效液相色谱法测定帕拉米韦原料药的含量。方法：非水滴定法：以无水冰醋酸为溶剂,0.1 mol/L的高氯酸滴定液为滴定剂,电位法指示滴定终点进行滴定。高效液相色谱法：采用Welch Ultimate AQ-C₁₈(150 mm×4.6 mm,5μm)色谱柱,以1 mmol/L磷酸二氢钾缓冲液(称取磷酸二氢钾约0.136 g溶于1 000 ml水,加入1 ml三乙胺,并以磷酸调pH 6.0)为流动相A,以乙腈为流动相B,90%A相等度洗脱10 min。流速为1.0 ml/min,柱温为40℃,检测器波长为210 nm,进样量为20μl。结果：两种方法均符合方法学验证要求。对同一批次样品进行测定,结果无显著性差异(P<0.05)。结论：两种方法均能用于帕拉米韦含量测定,为其质量控制提供依据,且各有优势。可根据实际情况和需求选择相应的方法。     

依帕司他原料药有关物质的HPLC测定方法改进研究

目的 采用改进的高效液相色谱法测定依帕司他原料药有关物质。方法 采用依利特Hypersil BDS C₁₈色谱柱（250 mm×4.6 mm,5 μm）,以乙腈-pH6.5磷酸盐缓冲液（0.025 mol·L^-1 KH₂PO₄+0.025 mol·L^-1 Na₂HPO₄,用H₃PO₄调节pH至6.5）为流动相,梯度洗脱,流速为1.0 mL·min^-1,检测波长为396 nm和280 nm,柱温为30℃,进样量为20 μL。结果 依帕司他与相邻杂质能较好地分离。立体异构体杂质在浓度0.010~30 μg·mL^-1内线性关系良好,检测限和定量限分别为0.80,2.4 ng·mL^-1。精密度、稳定性、准确度、耐用性均符合要求。结论 该方法可用于依帕司他原料药有关物质的检查。     

肾上腺素在碳糊电极上的吸附伏安测定法研究

为研究肾上腺素的电化学行为及其检测方法,在0.5mol·L^-1H₂SO₄底液中,用碳糊电极吸附伏安法测定肾上腺素,阳极峰电位为0.58V(vs.SCE),峰电位与肾上腺素的浓度在5.0×10^-9～1.0×10^-4mol·L^-1范围内呈良好的线性关系。此法检测下限为2.5×10^-9mol·L^-1,回收率为93.75%～103.33%,相对标准偏差为3.1%(n=12)。用本法对盐酸肾上腺素注射液进行了测定,获得满意结果。本文对反应机理进行了初步探讨,肾上腺素在碳糊电极上是一个两电子、两质子的不可逆过程。     

非水滴定与电位滴定法测定福尔可定含量的比较

目的对非水滴定和非水电位滴定法测定福尔可定的含量进行比较。方法均以冰醋酸为溶剂,非水滴定法采用结晶紫作为指示剂指示滴定终点,电位滴定法测定以第二个滴定突跃为滴定终点,两法均对滴定结果进行空白校正。结果电位滴定法滴定突跃明显,测定出的3批实际样品含量高于非水滴定的结果。结论因非水电位滴定法操作简单、滴定突跃明显,相较于非水滴定法能更好地控制福尔可定的质量。     

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.     

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.     

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.