HPLC法测定复方奥美沙坦氢氯噻嗪片的含量

目的:建立奥美沙坦氢氯噻嗪片中奥美沙坦酯与氢氯噻嗪的测定方法。方法:采用高效液相色谱法,色谱柱为ODS-C18柱(250 mm×4．6 mm,5μm);流动相为0．03 mol·L-1磷酸二氢钾溶液(用磷酸调至pH3．6)-乙腈(50:50),流速为1．0 mL·min-1;检测波长为271 nm。结果:奥美沙坦酯在7．89～71．03μg·mL-1范围内,峰面积与浓度呈良好的线性关系,r=0．999 9,平均回收率为99．7％(n=9);氢氯噻嗪在5．02～45．22μg·mL-1范围内,峰面积与浓度呈良好的线性关系,r=0．999 9,平均回收率为99．9％(n=9)。结论:该方法可同时用于奥美沙坦氢氯噻嗪片中奥美沙坦酯与氢氯噻嗪的质量控制。     

高效液相色谱法测定氢氯噻嗪片的含量

目的建立测定氢氯噻嗪片中氢氯噻嗪含量的高效液相色谱（HPLC）法。方法采用HypersilC18柱（150mm×4．6mm,5μm）,以乙腈-水（12：88）为流动相,流速为1．0mL／min。检测波长为271nm。结果氢氯噻嗪质量浓度线性范围为2．05～10．25μg／mL,r=0．99999（n=5）,平均回收率为98．48％,RSD=0．59％（12=6）。结论HPLC法准确、可靠,适用于测定氢氯噻嗪片中氢氯噻嗪的含量。     

复方卡托普利片中卡托普利和氢氯噻嗪的HPLC测定

建立了HPLC法同时测定复方卡托普利片中卡托普利和氢氯噻嗪的含量。采用C18柱，流动相为0．01mol／L磷酸二氢钠溶液-甲醇-乙腈(65：25：10，pH3．0)，检测波长229nm。卡托普利和氢氯噻嗪分别在48-576μg／ml(r=0．9994)和30～150μg／ml(r=0．9994)范围内浓度与峰面积成线性关系，平均回收率为100．4％(RSD=l.6％)和101．3％(RSD=1．9％)。     

HPLC法同时测定缬沙坦氢氯噻嗪胶囊中缬沙坦和氢氯噻嗪的含量

目的:建立同时测定缬沙坦氢氯噻嗪胶囊中缬沙坦和氢氯噻嗪含量的方法。方法:采用高效液相色谱法。色谱柱为Chromatrex C18,流动相为甲醇-水(70:30,用磷酸调pH=3.1),流速为1.0mL·min-1,检测波长为230nm,柱温为25℃,进样量为20μL。结果:缬沙坦和氢氯噻嗪的检测浓度线性范围分别为8～160(r=0.9997)、1.25～25(r=0.9995)μg·mL-1;平均加样回收率分别为99.66%、99.87%,RSD分别为0.33%、0.81%(n=9)。结论:所建立的分析方法快速、灵敏,结果准确可靠,可用于缬沙坦氢氯噻嗪胶囊的质量控制。     

UPLC法同时测定缬沙坦氢氯噻嗪片中缬沙坦和氢氯噻嗪的含量

目的:建立同时测定缬沙坦氢氯噻嗪片中缬沙坦和氢氯噻嗪含量的方法。方法:采用超高效液相色谱法。色谱柱为Phenomenex C_(18),流动相为[0.1%磷酸溶液-乙腈(95∶5,V/V)]-[0.1%磷酸溶液-乙腈(5∶95,V/V)](梯度洗脱),流速为0.25 mL/min,检测波长为272 nm,柱温为35℃,进样量为1.5μL。结果:缬沙坦和氢氯噻嗪检测质量浓度线性范围分别为8.1~324.2μg/mL(r=0.999 9)、1.2~50.1μg/mL(r=0.999 9);定量限分别为0.24、0.04 ng,检测限分别为0.06、0.01 ng;精密度、稳定性、重复性试验的RSD<2.0%;加样回收率分别为97.69%~100.35%(RSD=1.03%,n=9)、98.27%~100.60%(RSD=0.83%,n=9)。结论:该方法操作简单、快速,结果准确,可用于缬沙坦氢氯噻嗪片中缬沙坦和氢氯噻嗪含量的同时测定。     

高效液相色谱法测定复方卡托普利片剂中氢氯噻嗪含量

目的探讨测定复方卡托普利片剂中氢氯噻嗪含量的高效液相色谱（HPLC）法。方法色谱柱为Hypersil CN柱（150mm×4．6mm,5μm）,流动相为甲醇-四氢呋喃-水（10：10：80,以磷酸调pH至2．86）,流速为1．0mL／min,检测波长为220nm。结果氢氯噻嗪质量浓度在26-130μg／mL范围内与峰面积线性关系良好,线性回归方程为A=55432C＋110698,r=0．9999（n=5）;氢氯噻嗪的平均回收率为100．56％,RSD：0．46％（n=5）。结论所用方法快速简捷、可靠、准确度高、重现性好,可用于测定复方卡托普利片剂中氢氯噻嗪的含量。     

复方厄贝沙坦片中厄贝沙坦和氢氯噻嗪的HPLC测定

建立同时测定复方厄贝沙坦片中厄贝沙坦和氢氯噻嗪含量的HPLC方法。用Inertsil ODS-3色谱柱，流动相为乙腈-0．08mol／L磷酸溶液(用三乙胺调至pH5．0)(40：60)，检测波长225nm。厄贝沙坦和氢氯噻嗪分别在15～135μg／ml(r=0．9999)和1．2～10．8μg／ml(r=0．9999)浓度范围内线性关系良好，方法平均回收率分别为100．0％(RSD=0．46％)和100．5％(RSD=0．49％)。     

HPLC法测定富马酸比索洛尔氢氯噻嗪片中富马酸比索洛尔和氢氯噻嗪的含量

目的:采用高效液相色谱法测定富马酸比索洛尔氢氯噻嗪片中富马酸比索洛尔和氢氯噻嗪的含量。方法:以 C_(18)为色谱柱(5μm,4.6 mm×150mm),以磷酸盐缓冲溶液一乙腈(75:25)为流动相,柱温为40℃,检测波长为220 nm。结果:富马酸比索洛尔线性范围为25-300μg·mL~(-1),(r=0.9998),氢氯噻嗪线性范围为50-200μg·mL~(-1),(r=0.9965)。结论:方法简便,结果准确,适用于该产品的质量控制。     

反相高效液相色谱法测定氢氯噻嗪片含量

目的 :建立以反相高效液相色谱法测定氢氯噻嗪片含量的方法。方法 :以ZORBAXC18 为色谱柱 ,0 02mol/L磷酸盐缓冲液 -甲醇 (80∶20)为流动相 ,紫外检测波长为226nm ,柱温为室温 ,进样量为20μl。结果 :氢氯噻嗪在0 006～0 303mg/ml浓度范围内线性关系良好 (r=1 0000 ,n=5) ,平均回收率为100 1 % ,RSD=0 43 % (n=9)。结论 :该法准确度高、精密度好、简便快速 ,可作为氢氯噻嗪片的含量测定方法。     

厄贝沙坦氢氯噻嗪片中氢氯噻嗪人体生物等效性研究

目的：评价两种复方厄贝沙坦片中氢氯噻嗪的生物等效性。方法：20名健康男性志愿者分别单剂量po受试制剂和参比制剂，采用高效液相色谱-质谱联用法测定血浆中氢氯噻嗪的浓度并拟合药动学参数。结果：受试制剂和参比制剂在受试者体内的药动学参数如下：血浆中氢氯噻嗪的Cmax（72．6&#177;33．8）和（74．7&#177;31．9）ng&#183;ml^-1，tmax（2．0&#177;0．5）和（1．8&#177;0．4）h，t1／2（2．9&#177;1．2）和（2．5&#177;1．0）h，AUC0-48h（372．3&#177;168．7）和（377．5&#177;210．4）ng&#183;h&#183;ml^-1，AUC0-∞（398．3&#177;191．2）和（396．5&#177;223．5）ng&#183;h&#183;ml^-1。与参比制剂相比，受试制剂中氢氯噻嗪的平均相对生物利用度为（106．7&#177;26．1）％。结论：两种制剂中氢氯噻嗪具生物等效性。     

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.

---

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.