HPEC电位检测血浆中的长春胺

测定血液或血浆中长春胺(Vincamine)已报道的方法有TLC、GC 和MS 法等。后者灵敏度最高,可以测出血浆药物浓度低至30 Pg/ml。作者用装有电位检测器的HPL C测定血浆中长春胺的浓度可低至5 ng/ml,标准曲线于5～500 ng/ml 范围内呈线性。将由HPLC 分离后的长春胺氧化产生的电流对施加电位(+0.8到1.3V)每步距增加50 mV 进样一次)制图,得到色谱电位曲线图。在Lichrosorb RP-8色谱柱上分离长春胺,用乙腈-水(1:1),0.05 M 过氯酸锂为洗脱剂,流速1.2 ml/min。     

气相色谱氮磷检测器法测定人血浆毒鼠强浓度

目的建立测定人体血浆中毒鼠强(TET)浓度的毛细管气相色谱/氮磷检测器(GC/NPD)分析法。方法血浆中TET用乙酸乙酯作液-液提取,以乙酸乙酯为溶媒,载气为氦气,色谱柱为HP-5弹性石英毛细管柱,GC/NPD测定毒鼠强的浓度。结果在100~500 ng.mL-1浓度范围内线性关系良好,r=0.997 2(n=5),最低检测浓度为100ng.mL-1。TET血浆样品的低、中、高3个浓度(100,200和400 ng.mL-1)日内、日间变异系数(RSD)均≤10%,方法回收率均≥80%。结论该法操作简便,结果准确,可用于TET中毒的实验室鉴别和临床救治过程中的体内毒物浓度监测。     

用中空纤维液相微萃取-HPLC法测定人血浆中酒石酸美托洛尔的浓度

目的:建立中空纤维液相微萃取-HPLC法测定人血浆中酒石酸美托洛尔的浓度.方法:优化酒石酸美托洛尔液相微萃取法供给相和接受相的浓度、萃取时间、萃取温度、萃取转速和离子强度,血浆样品经中空纤维液相微萃取法萃取后,用HPLC法测定酒石酸美托洛尔的浓度.色谱柱:Agilent Zorbax Eclipse XDB-C18柱,流动相:甲醇-0.1％磷酸(40∶60),流速:1 ml/min,激发波长:227 nm,发射波长:305 nm,柱温:30℃.结果:酒石酸美托洛尔在2～ 125 ng/ml线性关系良好,低、中、高三种浓度(5、20、100 ng/ml)的日内、日间精密度均＜10％,回收率分别为(87.1±7.3)％、(92.6±5.8)％和(89.1±2.5)％.结论:中空纤维液相微萃取-HPLC法适用于测定血浆样品中酒石酸美托洛尔的浓度.     

高效液相色谱法测定人血浆中双氯芬酸钠的浓度

目的 :建立人血浆中双氯芬酸钠浓度的高效液相色谱测定方法。方法 :血样加乙腈去蛋白沉淀后 ,在Hypersil -BDS(250mm×4 6mm ,5μm)色谱柱上 ,以甲醇 -水 -10 %磷酸 (60∶40∶1)为流动相进行色谱分离 ,检测波长为276nm ,柱温为35℃。结果 :双氯芬酸钠浓度在20 50～2050 0ng/ml范围线性关系良好 (n=5,r=0 9998) ,最低检测浓度约为10ng/ml。低、中、高3种浓度的相对回收率为99 47 %～105 4 % ;日内相对标准差为3 77%～5 81 % (n=5) ,日间相对标准差为4 93 %～8 96% (n=5)。结论 :本法简便、快速 ,适合双氯芬酸钠药动学的研究     

RP-HPLC法同时测定血浆中艾司唑仑和阿普唑仑的浓度

目的　建立反相 HPL C法同时测定血浆中艾司唑仑 (EZ)和阿普唑仑 (AZ)浓度的方法。 方法 　以 Techsphere-ODS色谱柱为分析柱 ,甲醇 -水 (65∶ 3 5 )为流动相 ,硝西泮 (NZ)为内标 ,紫外 2 5 4nm处检测。结果 　 EZ和 AZ血浓线性范围为 0 .2 5～ 3 .0μg· ml- 1 ,最低检测浓度分别为 12 .5 ng/ml、12 .5 ng/ml,日内和日间精密度均小于 7%,平均回收率分别为 10 1.5 0 %,96.14 %。 结论 　本法可用于临床血药浓度测定     

RP-HPLC法测定大鼠血浆中的灯盏乙素含量

目的:建立大鼠血浆中灯盏乙素的RP-HPLC测定法.方法:RP-HPLC法,采用迪马C18柱(250 mm×4.6 mm,5 μm),甲醇-乙腈-0.01 mol/L乙酸铵溶液(pH 3.5)(22:8:70)为流动相,流速为1.0 ml/min,检测波长335 nm,柱温30 ℃.结果:线性范围为0.025～20.0 mg/L(r=0.999 9),最低定量浓度为25 ng/ml.结论:建立的大鼠血浆中灯盏乙素的反相液相色谱测定法灵敏、准确,可用于大鼠血浆中灯盏乙素浓度测定.     

LC-MS测定结直肠癌患者血浆中5-氟尿嘧啶浓度

目的建立LC-MS方法测定结直肠癌患者血浆中5-氟尿嘧啶(5-FU)浓度。方法采集晚期结直肠癌患者5-FU静脉泵注18~30 h的外周静脉血,以5-溴尿嘧啶(5-Br)为内标,Dikma-C_(18)反相色谱柱进行分离,流动相:甲醇-去离子水(45∶55);柱温:35℃;流速:0. 3 ml/min。以负离子模式(ESI-),选择性离子监测(SIR)检测5-FU血药浓度,计算患者AUC值。结果 5-FU在1 000~16. 8 ng/ml浓度范围内线性关系良好,最低检测限10 ng/ml。日内和日间精密度分别为2. 0%~8. 7%、2. 0%~8. 0%,提取回收率为93. 20%~99. 9%。结论本方法简单、快捷,适用于结直肠癌患者体内5-FU血药浓度测定。     

猪血浆中阿托品含量的毛细管气相色谱测定

采用气相色谱法测定猪血浆中阿托品的浓度。色谱柱为 HP- 5 (5 %苯基 - 95 %聚二甲基硅氧烷 )石英毛细管柱(30 m× 0 .5 3mm,1.5 μm) ,FID检测器。进样口温度 2 5 0°C,柱温 2 2 0°C,检测器温度 2 5 0°C。线性范围 0 .6 8～4 .2 5 μg/ m l(r=0 .9991) ,最低检测浓度 2 .5 ng/ ml     

人血浆中西酞普兰的HPLC-荧光法测定

建立了HPLC-荧光法测定人血浆中西酞普兰的浓度.血浆样品经液-液萃取后测定,用Zorbax SB C8色谱柱,磷酸二氢铵缓冲液(pH 3.5)-乙腈(65:35)为流动相,激发波长240 nm,发射波长302 nm.血浆中西酞普兰线性范围为1～100ng/ml,最低定量浓度为1ng/ml,日内、日间RSD均小于4.0%,方法平均回收率为93.2%.     

LC-MS/MS法测定人血浆及尿液中缬沙坦的浓度及其药动学研究

目的:建立测定人血浆及尿液中缬沙坦浓度的方法。方法:血浆样品经酸化后用乙醚提取浓度后进行分析;尿液样品直接稀释进样,均采用液相色谱-串联质谱(LC-MS/MS)法测定,色谱柱为Aglient ZORBAX SB-C18,流动相为0.1%甲酸-乙腈(梯度洗脱),流速0.2 ml/min。电喷雾离子源(ESI),正离子多反应监测模式测定,缬沙坦定量分析的离子对为m/z 436.4→253.2,定性分析离子对为m/z 436.4→291.3;内标氯沙坦定量分析的离子对为m/z 423.4→207.1,定性分析离子对为m/z 423.4→180.2。结果:血浆和尿液中缬沙坦的线性范围分别为4~5 000 ng/ml(r=0.998 5)、20~50 000 ng/ml(r=0.998 8);最低定量限分别为4、20 ng/ml;血浆萃取回收率为61.21%~70.30%;内标归一化基质效应因子的RSD分别为3.20%、11.21%;日内和日间RSD均≤8.34%。结论:所用方法快速、灵敏度高,适用于人血浆及尿液中缬沙坦的浓度测定及药动学研究。     

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.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

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.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.