利拉萘酯乳膏含量测定方法学的探讨

目的建立RP-HPLC法测定利拉萘酯乳膏中利拉萘酯的含量。方法采用Agilent C18色谱柱(150 mm×4.6 mm,5μm),流动相为乙腈-水(65∶35),柱温为35℃,检测波长为284 nm,流速为1.2 mL.min-1。结果利拉萘酯在40~200μg.mL-1与峰面积线性关系良好(r=0.999 9),平均回收率99.1%,RSD为0.86%。结论该方法简便、快速、准确、灵敏度高、重复性好,可用于利拉萘酯乳膏含量的测定。     

高效液相色谱法测定利拉萘酯乳膏的含量

目的:建立利拉萘酯乳膏的含量测定方法。方法:选用Angela C18色谱柱(25cm×4.6mm,5μm),流动相:甲醇-水(80:20);柱温40℃,流速:0.8ml·min-1,检测波长:281nm。结果:利拉萘酯线性范围8～32μg·ml-1(r=0.9996),回收率为99.3%(RSD为0.3%,n=9)。结论:本方法专属性强,可用于利拉萘酯的质量控制。     

利拉萘酯原料药的含量测定研究

目的建立高效液相色谱法测定利拉萘酯原料药的方法。方法选用Agilent C18色谱柱（20cm×4．6mm,5μm）,以甲醇-水（80：20）为流动相,柱温30℃,流速：1．0ml／min,检测波长：280nm。结果利拉萘酯的线性关系良好（16—24μg／ml,R2=0．9998）。结论本方法专属性强,流动相组成简单,便于利拉萘酯原料药的含量测定。     

HPLC法测定槲寄生胶囊中总黄酮醇苷的含量

目的 建立HPLC法测定槲寄生胶囊中总黄酮醇苷含量.方法 采用Kromasil C18(4.6×250 mm,5μm)色谱柱;流动相:甲醇-0.4%磷酸溶液(55:45);流速:1.0mL·min-1;测定检测波长为360nm.结果 槲皮素在浓度4.067μg·mL-1～40.67μg·mL-1范围内线性关系良好(r=0.9998):山萘素在浓度0.871μg·mL-1～8.71μg·mL-1范围内线性关系良好(r=0.9998);异鼠李素在浓度0.616μg·mL-1～6.16μgmL-1范围内线性关系良好(r=0.9996).结论 本方法简便、准确、专属性强,可测定槲寄生胶囊中总黄酮醇苷的含量.     

HPLC法测定盐酸氟桂利嗪分散片的血药浓度及药动学研究

目的:建立盐酸氟桂利嗪分散片体内血药浓度的HPLC测定方法,研究其药动学.方法:色谱柱为DiamodTM C18柱(150 mm×4.6 mm,5 μm);流动相为0.01 mol·L-1磷酸二氢铵缓冲液-甲醇(35:65),用磷酸调节pH至3.50.流速为1.0 mL·min-1,柱温为室温.荧光检测激发波长为254 nm,发射波长为308 nm.内标为对羟基苯甲酸丙酯.10例健康受试者服用盐酸氟桂利嗪分散片20 mg,采用HPLC法测定盐酸氟桂利嗪的血药浓度.结果:盐酸氟桂利嗪在1.5～100 ng·mL-1浓度内,其与内标的峰面积的比值与浓度呈良好的线性关系(r=0.999 8),低、中、高浓度的血浆标准样品的相对回收率在99.10%～101.88%,日内、日间RSD在1.99%～4.44%.盐酸氟桂利嗪分散片AUC0-t为(424.27±74.01)ng·h·mL-1,Cmax为(67.02±14.89)ng·mL-1,Tmax为(2.90±0.42)h,t1/2Ke为(9.73±3.15)h.结论:本试验提供了盐酸氟桂利嗪分散片体内血药浓度的HPLC测定方法及药动学参数,为临床应用提供了依据.     

HPLC测定丹参素冰片酯脂肪乳注射液含量及有关物质

目的:建立丹参素冰片酯脂肪乳注射液含量测定及有关物质检查方法。方法:采用高效液相色谱法。色谱柱:KromasilC18(150 mm×4.6 mm,5μm)色谱柱,流动相:乙腈-0.2%甲酸水(42︰58),流速为1.0 mL·min-1,检测波长280 nm,进样体积20μL。结果:试验结果表明,HPLC法检测主峰与杂质峰有较好的分离度,且重复性较好;丹参素冰片酯的浓度在5～60μg·mL-1范围内与峰面积呈良好线性关系(r=1.000),平均回收率为98.2%(n=9)。结论:该法操作简便,结果可靠,适用于丹参素冰片酯脂肪乳注射液含量测定及有关物质检查。     

LC-MS/MS法测定健康人血浆中的特比萘芬

目的:建立一种快速测定人血浆中特比萘芬血药浓度的LC-MS/MS法.方法:采用C18柱(4.6 mm×150 mm,5μm),柱温30℃,流动相为甲醇-水(含20 mmol·L-1乙酸铵)(95∶5),流速1.0 mL· min-1;气动辅助电喷雾离子化(ESI),正离子模式多反应离子检测(MRM);特比萘芬和内标(酮康唑)分别为:m/z 292.00→141.10,m/z 530.95→82.10.结果:特比萘芬在10.3～2054 ng·mL-1范围内线性关系良好(r=0.9978),定量下限10.27 ng·mL-1.特比萘芬低、中、高三个浓度批内及批间相对标准偏差、准确度、绝对回收率均符合方法学要求,无显著基质效应.结论:该方法专属性强、分析周期短,适合于临床上特比萘芬血浆含量的测定.     

高效液相色谱法测定醋酸甲萘氢醌片的含量

目的:建立反相高效液相色谱法测定醋酸甲萘氢醌片的含量.方法:色谱柱为KF-C18柱,以硝酸异山梨酯为内标物,流动相为甲醇-水(65:35),流速为1.0 mL·min-1,检测波长224 nm.结果:醋酸甲萘氢醌在0.02～0.18μg范围内线性关系良好(r=0.999 9).平均加样回收率为99.7%,RSD为0.4%.结论:本法结果准确、可靠,可用于该制剂的质量分析检验.     

HPLC法测定萘普生钠注射液的含量

目的 建立HPLC法测定萘普生钠注射液的含量的方法 .方法 高效液相色谱法.色谱柱为Kromasil C18柱(4.6mm×250mm,5μm);流动相以醋酸铵缓冲液(称取醋酸铵7.7g,加水50mL溶解,加冰醋酸6mL与适量水使成100mL)-甲醇(35:65);流速1.0mL·min-1;柱温:30℃;检测波长235nm.结果 该方法 在4.076～203.8μg·mL-1的浓度范围内线性关系良好(r＝0.9995,n＝6),平均回收率为99.83%,RSD＝0.21%(n＝6).结论 本方法 准确、简便、可靠,可用于萘普生钠注射液的含量测定.     

利拉萘酯喷雾剂的经皮渗透研究

目的 研究利拉萘酯喷雾剂的经皮渗透性。方法 采用改良Franz扩散池,以小型猪皮肤为渗透屏障,高效液相色谱法测定利拉萘酯含量。结果 利拉萘酯喷雾剂和乳膏剂的稳态透皮速率分别为(0.017±0.006),(0.014±0.003)μg·cm^-2·h^-1;利拉萘酯喷雾剂和乳膏剂的24 h累积渗透量分别为(0.60±0.23),(0.44±0.15)μg·cm^-2;利拉萘酯喷雾剂和乳膏剂在皮肤中的药物残留量分别为(8.2±1.3),(7.7±1.6)μg·g^-1。结论 利拉萘酯喷雾剂的稳态透皮速率、24 h累积渗透量、在皮肤中的药物残留量均稍大于利拉萘酯乳膏剂,但2种剂型之间没有显著性差异。     

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.     

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.