甲基多巴片在健康志愿者中的药动学

目的 :研究甲基多巴片在健康人体内的药动学过程 ,为临床用药提供参考。方法 :16名健康男性志愿者 ,单剂量口服甲基多巴片 2 5 0mg,在设计的时间点取静脉血 ,血药浓度采用高效液相色谱质谱法 (HPLC -MS)测定。由血药浓度数据计算主要药动学参数。结果 :单次服用 2 5 0mg甲基多巴片的药动学参数为AUC0→ 10 、Cmax、Tmax分别为 (7± 4 )mg·h·L-1,(1.7±0 .9)mg·L-1,(2 .5± 0 .9)h。结论 :甲基多巴片剂在我国健康人群中的药动学与国外报道相似     

毛细管色谱法测定唑尼沙胺中的有机溶剂残留量

目的建立毛细管气相色谱法测定唑尼沙胺中的有机溶剂残留量。方法用DB-624毛细管气相色谱柱,FID检测器,以正丙醇为内标进行测定。结果甲醇、乙醇、乙酸乙酯、乙酸的线性范围分别为15.029~240.464 mg.L-1(r=0.999 9)、24.964~399.424 mg.L-1(r=1)、25.02~400.32 mg.L-1(r=0.999 9)、24.99~399.84 mg.L-1(r=0.999 9);甲醇、乙醇、乙酸乙酯、乙酸的平均回收率分别为99.5%、99.0%、98.9%、99.2%;RSD分别为1.2%、1.4%、1.2%、1.5%1(n=9)。结论方法简单、灵敏、准确、重现性好,适用于唑尼沙胺中的有机溶剂残留量的测定。     

毛细管气相色谱法测定普拉格雷中的有机溶剂残留量

目的建立毛细管气相色谱法测定普拉格雷中的有机溶剂残留量。方法用DB624毛细管气相色谱柱,FID检测器,以丙酮为内标进行测定。结果乙醇、乙醚、二氯甲烷、乙酸乙酯的线性范围分别为50～800(r=0.999 5)、50～800(r=0.999 1)、6～96(r=0.999 4)、50～800 mg.L-1(r=0.999 6);乙醇、乙醚、二氯甲烷、乙酸乙酯的平均回收率分别为99.51%、98.97%、99.25%、99.32%;RSD为1.25%、1.14%、1.23%、1.05%(n=9)。结论本方法适用于普拉格雷中的有机溶剂残留量的测定。     

毛细管色谱法测定盐酸米多君中的有机溶剂残留量

目的建立毛细管气相色谱法测定盐酸米多君中的有机溶剂残留量。方法用HP-FFAP毛细管气相色谱柱,FID检测器,以正丙醇为内标进行测定。结果乙醇、乙腈、乙酸的线性范围分别为20～800μg.L-1(r=0.999 9)、1.64～65.6μg.L-1(r=0.999 7)、20～800μg.L-1(r=0.999 5),平均回收率分别为100.2%、99.7%、99.6%,RSD分别为0.74%、1.17%、1.37%(n=9)。结论本方法简单、准确、灵敏度高、重现性好,适用于盐酸米多君中有机溶剂残留量的测定。     

GC和GC-MS法测定注射用大豆油中脂肪酸组成及含量

目的分析注射用大豆油中主要脂肪酸组成,并建立同时测定大豆油中棕榈酸、硬脂酸、油酸和亚油酸4种成分含量的方法。方法采用GC-MS法确定大豆油中4种主要脂肪酸组成,采用毛细管气相色谱法测定甲酯化后大豆油中棕榈酸、硬脂酸、油酸和亚油酸的含量。结果棕榈酸甲酯、硬脂酸甲酯、油酸甲酯和亚油酸甲酯的线性范围分别为0.508 0⁸.128g·L-1(r=0.999 0)、0.126 08.128g·L-1(r=0.999 0)、0.126 0².016g·L-1(r=0.999 4)、1.0072.016g·L-1(r=0.999 4)、1.007¹6.11g·L-1(r=0.999 4)和2.52216.11g·L-1(r=0.999 4)和2.522⁴0.34g·L-1(r=0.999 4);各成分的平均回收率分别为(100.8±0.64)%、(101.6±0.89)%、(100.5±0.31)%和(99.4±0.84)%,RSD分别为1.36%、0.68%、1.11%和1.03%(n=9)。结论确定了4种主要脂肪酸组成,建立了采用内标法对注射用大豆油中4种脂肪酸进行含量测定,该方法准确可靠,可为注射用大豆油的质量评价提供依据。     

毛细管气相色谱法测定乙酰化羊毛脂中的有机溶剂残留量

目的:建立毛细管气相色谱法测定药用辅料乙酰化羊毛脂中的有机溶剂残留量。方法:用HP-FFAP毛细管气相色谱柱,FID检测器,以二氧六环为内标进行测定。结果:正庚烷、二氯甲烷、吡啶、冰醋酸的线性范围分别为40~800 mg.L-1(r=0.9998)、4.8~96 mg.L-1(r=0.9999)、1.6~32 mg.L-1(r=0.9999)、40~800 mg.L-1(r=0.9998)。正庚烷、二氯甲烷、吡啶、冰醋酸的平均回收率(n=9)分别为99.2%,99.7%,100.1%,99.5%。结论:该方法简单、灵敏、准确,重现性好,适用于乙酰化羊毛脂中的有机溶剂残留量的测定。     

顶空毛细管气相色谱法测定盐酸莫雷西嗪中残留溶剂的含量

目的建立顶空气相色谱法测定盐酸莫雷西嗪中甲醇、乙醇、异丙醇、二氯甲烷、乙酸乙酯、四氢呋喃、甲苯7种有机溶剂残留量的方法。方法色谱柱为DB-624石英毛细管柱,柱温采用程序升温,检测器为FID检测器,检测器温度为250℃,进样口温度为150℃,以水为溶解介质。结果甲醇、乙醇、异丙醇、二氯甲烷、乙酸乙酯、四氢呋喃、甲苯的质量浓度的线性范围分别为12.0~240 mg.L-1(r=1.000 0)、10.0~200 mg.L-1(r=0.999 9)、10.0~200 mg.L-1(r=0.999 9)、1.20~24 mg.L-1(r=0.999 9)、10.0~200 mg.L-1(r=0.999 9)、1.44~28.8 mg.L-1(r=0.999 8)、1.78~35.6 mg.L-1(r=0.999 7);平均回收率为98.1%~99.5%(RSD=0.6%~1.7%);定量限为0.22~11.91 mg.L-1;3批样品中7种有机溶剂残留量均符合《中华人民共和国药典》要求。结论本方法简单、准确、灵敏度高、重现性好,可用于该药物中有机溶剂残留量的测定。     

高效液相色谱法测定盆炎灵合剂中的阿魏酸、延胡索乙素、芍药苷、丹酚酸B及原儿茶醛含量

目的采用高效液相色谱法同时测定盆炎灵合剂中阿魏酸、延胡索乙素、芍药苷、丹酚酸B和原儿茶醛等成分的含量。方法 Hypersil ODS2色谱柱(4.6 mm×250 mm,5μm);流速:1.0 m L·min-1;流动相A为乙腈,流动相B为0.1%磷酸溶液,梯度洗脱。结果阿魏酸、延胡索乙素、芍药苷、丹酚酸B和原儿茶醛质量浓度分别在0.008 4⁰.168 4 mg·m L-1(r=0.999 9)、0.023 60.168 4 mg·m L-1(r=0.999 9)、0.023 6⁰.471 2 mg·m L-1(r=0.999 3)、0.030 40.471 2 mg·m L-1(r=0.999 3)、0.030 4⁰.304 0 mg·m L-1(r=0.999 7)、0.031 30.304 0 mg·m L-1(r=0.999 7)、0.031 3⁰.625 4 mg·m L-1(r=0.999 9)、0.010 10.625 4 mg·m L-1(r=0.999 9)、0.010 1⁰.202 8 mg·m L-1(r=0.999 9)与其峰面积呈良好的线性关系;平均加样回收率分别为103.9%、96.5%、96.8%、98.7%和101.5%,RSD值分别为1.7%、2.0%、2.5%、2.0%和2.2%(n=6)。结论该方法线性、重复性、精密度、加样回收率均符合要求,可作为盆炎灵合剂的含量控制方法。     

气相色谱法测定恩替卡韦原料药中有机溶剂残留量

目的建立毛细管气相色谱法测定抗病毒原料药恩替卡韦中的有机溶剂残留量。方法采用DB-624毛细管色谱柱,FID检测器。载气为N2,流速为2ml·rain-1,进样口温度250℃,检测器温度为250℃。结果甲醇、二氯甲烷、正己烷、乙酸乙酯、四氢呋喃、三乙胺、甲苯和苯甲醇的线性范围分别为0．06018～0．6018g·L-1（r=0．9973）、0．01202～0．1202g·L-1（r=0．9968）、0．00578～0．0578g·L-1（r=0．9972）、0．10348～1．0348g·L-1（r=0．9972）、0．01706-0．1706g·L-1（r=0．9968）、0．10126～1．0126g·L-1（r=0．9957）、0．01806-0．1806g·L-1（r=0．9983）和0．10074～1．0074g·L-1（r=0．9993）;平均回收率（n=9）分别为98．6％（RSD：2．36％）、95．5％（RSD=5．98％）、96．9％（RSD=4．36％）、100．5％（RSD=2．02％）、102．3％（RSD=3．86％）、100．1％（RSD=1．56％）、102．4％（RSD=1．88％）、99．4％（RSD=1．63％）。结论该方法操作简便、准确、灵敏度高、重复性好,适用于恩替卡韦原料药中有机溶剂残留量的测定。     

毛细管色谱法测定替莫唑胺酯中的有机溶剂残留量

目的建立毛细管气相色谱法测定替莫唑胺酯中的有机溶剂残留量。方法采用INNOWax毛细管气相色谱柱、FID检测器,以乙腈为内标进行测定。结果正己醇、丙酮、乙酸乙酯、异丙醇、正己烷、吡啶的线性范围分别为25～400μg.L-1(r=0.999 6)、25～400μg.L-1(r=0.999 9)、25～400μg.L-1(r=0.999 9)、25～400μg.L-1(r=0.999 7)、1.45～23.2μg.L-1(r=0.999 8)和1～16μg.L-1(r=0.999 3);正己醇、丙酮、乙酸乙酯、异丙醇、正己烷、吡啶的平均回收率分别为99.7%、100.3%、100.2%、100.4%、99.9%和100.3%;RSD分别为1.11%、1.43%、1.47%、1.37%、1.59%和1.47%(n=9)。结论该方法简单、灵敏、准确、重现性好,适用于替莫唑胺酯中的有机溶剂残留量的测定。     

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.     

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.     

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.