气相色谱法测定环孢素口服溶液中乙醇和丙二醇含量

目的：建立气相毛细管色谱法测定环孢素口服溶液中的乙醇和丙二醇含量;方法：色谱柱为TG-624(30 m × 0.25 mm × 1.4 μm),采用程序升温;进样口温度：200 ℃;检测器温度：220 ℃;柱流量：0.2 ml.min^-1;进样量：1 μl;进样方式：分流;分流比：20:1;载气：氮气;内标物为正丙醇,溶剂为二甲基亚砜。结果：乙醇在1.491 mg.ml^-1～3.479 mg.ml^-1的范围内,其峰面积与浓度呈良好线性关系,y=0.5376x-0.0422, r=0.9999;高、中、低三个浓度的加样回收率分别为99.6%、100.8%、99.5%;定量限为19.9 mg.ml^-1,检测限为6.0 mg.ml^-1;重复性和中间精密度的RSD分别为0.04%﹑0.33%。丙二醇在1.4639 mg.ml^-1～3.4157 mg.ml^-1的范围内线性关系良好,y=0.3924x-0.0152, r =0.9997;高、中、低三个浓度的加样回收率分别为101.3%、100.5%、100.6%;定量限为19.5 mg.ml^-1,检测限为5.8 mg.ml^-1;重复性和中间精密度的RSD分别为0.60%﹑0.74%。结论：经验证,该方法简便易行,线性、专属性、耐用性、精密度、稳定性良好,可用于测定环孢素口服溶液中乙醇和丙二醇含量。     

GC直接进样和顶空进样法测定碘酊中乙醇浓度

目的 建立一气相色潽法,分别采用顶空进样和液体进样器进样的方法测定碘酊中乙醇的含量,并对两种进样方式进行比较研究。 方法 采用安捷伦DB-ALC1型气相色谱柱(30 m×0.53 mm,3.0μm),FID检测器温度：250℃,柱温：80℃,进样口温度：200℃,载气：N₂,柱流速：5 ml.min_-1,辅助加热区115℃。以叔丁醇为内标进行定量,采用顶空和液体进样两种方式,液体进样量 1.0μl,顶空进样量1.0 mL。结果 顶空进样时,乙醇在15.78~63.12 mg.ml_-1浓度范围线性关系良好,Y=3.5589X-0.3413(R₂=0.9989);平均回收率≥96.55%,RSD≤4.30%;日内精密度RSD≤3.86%;液体进样时,乙醇在15.78~63.12 mg.ml_-1浓度范围线性关系良好,Y=0.015X-0.006(R₂=0.9995);平均回收率≥98.20%,RSD≤3.22%;日内精密度RSD≤3.85%。结论 这两种方法均能准确地测量碘酊中乙醇的浓度,顶空进样法耗时较长但灵敏度比直接进样更高,对色谱柱的污染也较小,两种方法均能用于碘酊中乙醇含量的测定。     

顶空气相色谱法测定丹酚酸B中有机溶剂残留量

摘 要 目的： 建立丹酚酸B原料药中3种残留溶剂的测定方法。 方法: 采用顶空毛细管气相色谱法测定,色谱柱为HP 5毛细管柱（30 m×0.32 mm,0.6 μm),进样口温度为180℃,进样量为0.1 ml,分流比为1∶10;柱温为40 ℃保持6 min,15 ℃·min^-1升温至180 ℃,保持5 min;检测器为FID,温度：250℃;载气：N2,流速：1.7 ml·min^-1。二甲亚砜（DMSO）为溶剂。结果:各残留溶剂均可达到基线分离。各残留溶剂乙醇、丙酮和乙酸乙酯分别在12.650～1.012×103 μg·ml^-1(r=0.999 3)、12.750～1.020×103 μg·ml^-1(r=0.999 7)、12.550～1.004×103 μg·ml^-1(r=0.999 7)范围内线性关系良好。乙醇、丙酮、乙酸乙酯的平均回收率分别为96.89%（RSD=3.81％,n=9）、99.56%（RSD=4.05％,n=9）、97.21%（RSD=4.95％,n=9）。结论: 该法操作简便,重复性好,结果准确可靠,可以用于丹酚酸B原料药中残留溶剂的测定。     

HPLC法同时测定妇科千金片中6种活性成分

摘 要 目的：建立HPLC 法同时测定妇科千金片中阿魏酸、绿原酸、盐酸小檗碱、穿心莲内酯、脱水穿心莲内酯及党参炔苷等6种活性成分,为妇科千金片质量提供保障。方法: 采用Waters XBridgeTM C₁₈柱（250 mm×4.6 mm,5 μm）色谱柱;流动相为0.1%磷酸水溶液 乙腈,梯度洗脱,流速1.0 ml·min^-1;紫外检测波长为326,316,225,254,268 nm;柱温：35℃;进样量为10 μl。结果: 阿魏酸、绿原酸、盐酸小檗碱、穿心莲内酯、脱水穿心莲内酯及党参炔苷的线性范围分别为0.709～28.360 μg·ml^-1,0.459～18.350 μg·ml^-1,0.510～20.380 μg·ml^-1,1.259～50.360μg·ml^-1,0.829～33.140 μg·ml^-1,1.709～68.340 μg·ml^-1;平均加样回收率分别为99.5%,99.85%,98.8%,99.4%,98.5%,98.9%（n=6）,RSD分别为0.4%,0.1%、0.7%、0.5%、0.9%、0.4%（n=6）。结论:该方法平均回收率高、简便可行、灵敏度高、重复性好,可用于控制妇科千金片中阿魏酸、绿原酸、盐酸小檗碱、穿心莲内酯、脱水穿心莲内酯及党参炔苷的质量控制。     

GC测定健儿清解液中6个挥发性成分的含量

目的 测定不同厂家生产的健儿清解液中挥发油成分糠醛、樟脑、苯甲醛、4-萜品醇、α-松油醇和龙脑的含量。方法 采用HP-INNOWAX毛细管柱为分离柱,以环己酮为内标,程序升温,进样口温度200 ℃,检测器：FID,温度220 ℃。结果 糠醛、樟脑、苯甲醛、4-萜品醇、α-松油醇和龙脑的线性范围分别为5.139～128.467 μg?ml_^-1(r=0.99990),1.900～47.500 μg?ml_^-1(r=0.99937),6.537～163.436 μg?ml_^-1(r=0.99996),1.057～26.423 μg?ml_^-1(r=0.99938),2.398～59.958 μg?ml_^-1(r=0.99923),1.014～25.346 μg?ml_^-1(r=0.99936);该方法的回收率分别为97.0%,99.3%,98.6%,94.6%,93.5%,101.2%。不同厂家生产的健儿清解液中上述成分含量存在较大差别。结论 该方法可为健儿清解液质量标准的提高提供科学数据。     

HPLC法同时测定舒血灵胶囊中三七皂苷R1、人参皂苷RG1及人参皂苷Rb1的含量

摘 要 目的： 建立舒血灵胶囊中三七皂苷R₁、人参皂苷RG₁及人参皂苷Rb₁的含量测定方法。方法: 采用Hypersil ODS-2 C₁₈（250 mm×4.6 mm, 5 μm）色谱柱;以乙腈(A)-水(B)为流动相进行梯度洗脱,流动相梯度为：0～8 min,20%A→20%A,8～40 min,20%A→30%A,40～60 min,30%A→45%A;流速：1.0 ml·min^-1;柱温：25℃;检测波长：203 nm;进样量：20 μl。结果: 三七皂苷R₁在浓度0.05～0.50 mg·ml^-1范围内,人参皂苷RG₁和Rb₁在浓度0.20～2.00 mg·ml^-1范围内,与峰面积呈较好的线性关系（r=0.999 9）;三种成分的平均加样回收率分别为98.79%、98.42%、98.89%,RSD分别为0.85%、0.97%、0.74%（n=6）;日内精密度分别为0.49%、0.20%和0.39%;日间精密度分别为0.75%、0.56%和0.51%;稳定性、重复性试验的RSD<1%。结论:本试验建立的测定方法简便、准确性高、重复性好,可用于该制剂的含量测定。     

GC测定香砂平胃丸中苍术素、厚朴酚、和厚朴酚的含量

摘 要 目的： 建立香砂平胃丸中苍术素、厚朴酚、和厚朴酚的气相色谱含量测定方法。方法: ：采用HP-5毛细管柱（30 m×0.32 mm×0.25μm）,以氮气为载气,流速为2.0 ml·min^-1,进样口温度为300℃,检测器(FID)温度为300℃,进样量为1 μl,分流比为20∶1;采用程序升温模式,起始温度为100℃,保持7 min,以20℃·min^-1的速率升温至250℃,保持10 min。结果: 苍术素、厚朴酚、和厚朴酚分别在4.264～85.280 μg·ml^-1（r=0.999 7）、9.856～197.120 μg·ml^-1（r=0.999 5）、10.040～200.800 μg·ml^-1（r=0.999 6）范围内线性关系良好,平均回收率分别为98.2%、98.6%、99.3%,RSD分别为1.5%、1.5%、1.9%（n=6）。结论:该方法简便、准确、可靠,可用于香砂平胃丸的质量控制。     

二甲双胍缓释片人体药代动力学及其相对生物利用度

目的 研究国产盐酸二甲双胍缓释片在人体药代动力学行为并与普通片进行等效性评价比较,并估算其药代动力学参数。方法 20名受试者分两组交叉服用缓释片和普通片,用RP-HPLC法测定血浆中药物浓度,并估算相应的药动学参数。结果 单剂量口服1000mg缓释片和普通片后估算的AUC_0-24分别为11.95±2.62μg·h^-1·ml^-1和10.72±2.23μg·h^-1·ml^-1;C_max分别为1.50±0.22μg·ml^-1和2.34±0.30μg·ml^-1;T_max分别为3.38±0.8h和1.61±0.32h;t_1/2分别为4.94±0.47h和3.20±0.38h;多剂量1000mg·d^-1时AUC_ss分别为15.04±3.01μg·h^-1·ml^-1和14.51±2.69μg·h^-1·ml^-1;C_max分别为1.68±0.25μg·ml^-1和1.60±0.26μg·ml^-1;C_min分别为0.15±0.03μg·ml^-1和0.12±0.04μg·ml^-1;Cav分别为0.62±0.13μg·ml^-1和0.61±0.11μg·ml^-1;T_max分别为3.61±0.60h和1.88±0.38h;AUC_0-24和AUC_ss经对数转换后方差分析和双单侧t检验，显示两制剂吸收程度生物等效。结论受试制剂和参比制剂吸收程度生物等效，但具有缓释特性。盐酸二甲双胍缓释片的相对生物利用度单剂量时为（111.5±8.3）%，多剂量时为（103.6±9.2）%。     

气相色谱法测定牛黄清心丸（局方）中龙脑和异龙脑含量

摘 要 目的：建立气相色谱法测定牛黄清心丸（局方）中龙脑和异龙脑含量的方法。方法: 采用HP INNOWAX毛细管柱（30 m×0.25 mm,0.25 μm）,柱温110 ℃,进样口温度200 ℃;FID检测器温度230 ℃;载气为氮气;载气流速1.8 ml·min^-1,分流比10∶1;进样量：1 μl。结果:龙脑和异龙脑分别在0.01～5.09 μg·ml^-1（r=0.999 5）和0.01～5.03 μg·ml^-1（r=0.999 1）范围内线性关系良好,平均回收率分别为99.34%和99.24%,RSD分别为0.59%和0.62% （n=6）。结论:所建方法准确、灵敏、简便,可用于牛黄清心丸（局方）的质量控制。     

HPLC法同时测定四季感冒胶囊中橙皮苷和连翘苷的含量

摘 要 目的： 建立四季感冒胶囊中橙皮苷和连翘苷的含量测定方法。方法: 应用高效液相色谱法测定,色谱柱为Agilent-XDB C₁₈(250 mm×4.6 mm,5 μm),流动相为甲醇-0.1%磷酸,梯度洗脱,流速为1.0 ml·min^-1,柱温为30℃,检测波长为277 nm,进样量为5 μl。结果:橙皮苷和连翘苷的线性范围分别为12.000～60.000 μg·ml^-1(r=0.999 6)、18.000～90.000 μg·ml^-1(r=0.999 3);平均加样回收率分别为96.61%(RSD=1.40%),97.66%(RSD=1.27%)。结论: 该方法简便易行、准确、重复性好,可用于四季感冒胶囊的含量控制。     

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.     

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.