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。     

高效液相色谱法测定盐酸多塞平片含量

目的 建立测定盐酸多塞平片含量的 方法 . 方法 采用高效液相色谱法. 色谱柱：Shimpack C18（150 mm×6 mm,5 μm）,流动相：甲醇-乙腈-0.02 mol•L-1磷酸二氢钾溶液（35：20：45）,波长：297 nm,流速：1.0 mL•min-1,柱温：室温,进样量：20 μL. 结果 多塞平浓度在55～330 μg•mL-1范围内呈良好的线性关系（r＝0.999 6,n＝6）,平均回收率为99.79%,RSD＝0.35%（n＝6）. 结论 该 方法 简便、快速, 结果 准确,灵敏度高,重复性好,可作为盐酸多塞平片含量测定的 方法 .     

虫草保元胶囊中西红花苷-Ⅰ和西红花苷-Ⅱ含量测定

目的采用高效液相色谱法测定虫草保元胶囊中西红花苷 Ⅰ和西红花苷 Ⅱ的含量。方法色谱柱为Hypersil ODS2 C18柱（150 mm×4.6 mm,5 μm）,流动相为甲醇：水（48：52）,检测波长：440 nm;柱温室温,流速：1.0 mL•min－1。结果西红花苷 Ⅰ在6～45 μg•mL－1浓度范围内线性关系良好,r＝1.000 0,平均回收率98.73%,RSD为1.24%（n＝6）;西红花苷 Ⅱ在3.2～24.0 μg•mL－1浓度范围内线性关系良好,r＝1.000 0,平均回收率98.01 %,RSD为1.53 %（n＝6）。结论该方法操作简便,测定结果准确,重复性好,可用于虫草保元胶囊的质量控制。     

复方醋酸曲安奈德搽剂中醋酸曲安奈德含量测定

目的建立测定复方醋酸曲安奈德搽剂中醋酸曲安奈德含量的高效液相色谱法。方法用Welch Materials Ultimate XB C8 （250 mm×4.6 mm,5 μm）色谱柱;流动相为甲醇 水（60：40）;流速为1.0 mL•min－1;检测波长为240 nm。 结果醋酸曲安奈德在12～32 μg•mL－1的浓度范围内呈现良好的线性关系,相关系数为0.999 9;日内精密度为0.33%（n＝6）;平均回收率为99.8%（n＝9）。结论该方法快捷方便,结果可靠,可作为复方醋酸曲安奈德搽剂的质量控制标准。     

反相高效液相色谱法同时测定复方加地滴眼液中两种成分的含量

［摘要］目的建立反相高效液相色谱法测定复方加地滴眼液中加替沙星和地塞米松磷酸钠的含量。方法色谱柱：Shodex Rspak DE C18 柱（150 mm×4.6 mm,5 μm）;流动相：甲醇（A） 0.02 mol•L 1磷酸溶液（B）（三乙胺调pH值3.5）,梯度洗脱。结果加替沙星浓度在20.0～200.0 μg•mL 1（r＝0.999 6）、地塞米松磷酸钠浓度在2.5～25.0 μg•mL 1（r＝0.999 5）范围内与峰面积呈良好的线性关系,平均回收率（n=9）分别为99.4%（RSD=0.66%）和99.6%（RSD=0.89%）。结论该方法简便、准确、重复性好,可用于同时测定复方加地滴眼液中两组分的含量。     

高效液相梯度洗脱法同时测定复方诺氟沙星滴耳液中3组分的含量

（1. ［摘要］目的建立高效液相色谱（HPLC）法同时测定复方诺氟沙星滴耳液中诺氟沙星、甲硝唑和丙酸倍氯米松的含量。方法Kromasil C18 柱（4.6 mm×250 mm, 5 μm）,流动相为甲醇 乙腈 0.025 mol•L 1磷酸溶液（用三乙胺调至pH至3.0） 注射用水,梯度洗脱。结果诺氟沙星、甲硝唑和丙酸倍氯米松的线性范围分别为15.0～150.0 μg•mL 1（r＝0.999 4）, 15.1～151.0 μg•mL 1（r＝0.999 3）和2.6～ 26.0 μg•mL 1（r＝0.999 4）;平均回收率分别为99.5%, 99.7%和99.5%;RSD分别为0.80%,0.78%和0.92%（n＝9）。结论该方法操作简便,快速,准确度较高,适合复方诺氟沙星滴耳液含量测定。     

复方罗红霉素片多剂量给药在健康志愿者体内的药动学

目的研究复方罗红霉素片多剂量给药在健康志愿者体内的药动学。方法24例健康成年志愿者,男女各半,采用随机分组平行设计,分别多剂量口服复方罗红霉素片、罗红霉素片150 mg＋盐酸氨溴索片30 mg,采用串联质谱法测定血浆中罗红霉素和氨溴索的浓度,采用DAS2.1程序分别计算各受试者的药动学参数,并用配对t检验对罗红霉素或氨溴索进行分析。结果复方罗红霉素片组与两单药合用组相比,罗红霉素和氨溴索的人体药动学参数均差异无统计学意义,复方罗红霉素片中罗红霉素和氨溴索的主要药动学参数Cmax分别为（6 261.67±2 111.12）和（51.42±19.83） ng•mL 1,t1/2分别为（14.70±8.91）和（10.19±1.94） h,AUC0→t分别为（96 055.25±38 428.39）和（679.86±183.90） μg•L 1•h,AUCss分别为（47 767.15±16 097.92）和（372.53±119.18） μg•L 1•h。结论多剂量给予复方罗红霉素片后,与两单药合用的对照药的药动学特征差异无统计学意义。     

不同产地柚子中柚皮苷的含量测定

摘要目的测定不同产地柚子果皮果肉中柚皮苷的含量。方法采用高效液相色谱（HPLC）法,色谱柱为Zorbax Eclipse XDB C18（4.6 mm×150 mm,5 μm）。流动相为甲醇 水（30：70）,流速为1.0 mL•min－1,检测波长为270 nm。结果柚皮苷在11.0～220.0 μg•mL－1浓度范围内与峰面积积分值呈良好线性关系（r＝0.999 7）;加样回收率为98.8%（RSD＝1.52%）。其中柚皮苷含量最高的是新鲜的玉环蜜柚果皮（10 396.75 μg•g－1）。结论该方法简便,快速,灵敏,准确,稳定性,重复性好,可用于柚皮中柚皮苷的测定。     

高效液相色谱法测定银黄清肺胶囊中盐酸麻黄碱含量

［摘要］目的用高效液相色谱法测定银黄清肺胶囊中盐酸麻黄碱的含量。方法采用Aglient C18(250 mm×4.6 mm,5 μm)色谱柱;流动相：乙腈 0.1%磷酸溶液(5：95);流速：1.0 mL•min 1;柱温35 ℃;检测波长：210 nm。结果盐酸麻黄碱的质量浓度范围9.379 2～93.792 0 μg•mL 1,r=0.999 5(n=6),平均回收率98.11%,RSD=1.21%(n=9)。结论该方法灵敏度高,重复性好,适用于盐酸麻黄碱的含量测定。     

二妙丸中苍术素含量测定

目的建立测定二妙丸中苍术素含量的反相高效液相色谱法。方法Agilent HC C18 Analytical （250 mm×4.6 mm,5 μm）色谱柱;以乙腈和水梯度洗脱,流速为1.0 mL•min－1;检测波长340 nm;柱温30 ℃;进样量10 μL。结果苍术素在6.08～30.40 μg•mL－1浓度范围内具有良好的线性关系,r＝0.999 8,苍术素平均回收率为99.6%,RSD＝1.9%（n＝9）。结论该方法简便,准确,重复性好,适用于二妙丸中苍术素含量测定。     

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.