氢化物发生-原子荧光法同时测定六味地黄丸中的砷和汞

目的 :建立六味地黄丸中砷 (AS)和汞 (Hg)同时测定的方法。方法 :采用AFS - 2 30型双道原子荧光光度计 ,以 15 g·L-1硼氢化钠作还原剂 ,1mol·L-1盐酸作载流进行测定。结果 :线性范围砷为 0 .5～ 10 0 μg·L-1,汞为 0 .1～ 6 0 μg·L-1;检出限砷为 0 .0 2 μg·L-1,汞为 0 .0 1g·L-1;加样回收率分别在 99.0 %～ 10 6 .0 % (砷 ) ,89.1%～ 96 .3% (汞 )之间 ,RSD <3.5 % (n =10 )。结论 :方法简便快速 ,结果准确可靠 ,可望作为中成药中重金属元素分析的常规实验方法。     

高效液相色谱法测定人血浆中洛沙平的浓度

目的建立测定人血浆中洛沙平浓度的HPLC法.方法以DiamonsilTM C18反相柱(250 mm×4.6 mm,5 μm)为色谱柱,流动相为甲醇-0.03 mol·L-1醋酸铵(8713),流速为0.8 mL·min-1,检测波长257 nm,以乙醚为提取剂.结果洛沙平的高(585.6 μg·L-1)、中(292.8μg·L-1)、低(36.6 μg·L-1)3个浓度的平均回收率分别为95.29%,96.77%,97.89%,日内(n=5)、日间(n=3)RSD均小于6%;分析方法的最低定量限为6.1 μg·L-1.线性范围为6.1～732.0μg·L-1,回归方程为C=562.72F-30.33,r=0.999 3(n=9).结论该方法灵敏、准确、简单、快速,可用于临床血药浓度监测和药动学研究.     

高效液相色谱法同时检测人血清中全反式及13—顺式维甲酸浓度

目的 :建立高效液相色谱方法同时检测人血清中全反式及 13 -顺式维甲酸浓度。方法 :色谱柱 :μBondapakC18(3 9mm× 30 0mm) ,流动相 :甲醇 -醋酸铵缓冲液 (85∶15 ) ,流速 :0 8mL·min-1,紫外检测波长 :340nm ,柱温 :2 2℃ ,血清样品经乙醚 2次提取 ,按内标法定量 ,内标物选用对二甲氨基苯甲醛。结果 :全反式及 13-顺式维甲酸的线性范围分别在 0 8～ 112 0 μg·L-1和 0 82～ 1312 μg·L-1,最低检测浓度均为 0 6μg·L-1。全反式维甲酸测定的平均回收率为 98 86 %～ 10 5 2 % ,日内、日间精密度RSD为 0 84%～ 5 5 % ,13-顺式维甲酸测定的平均回收率为 10 1 6 %～ 10 1 8% ,日内、日间精密度RSD为 1 4%～ 5 7%。结论 :本方法灵敏、准确 ,样品处理简便易行 ,适用于全反式维甲酸的临床药动学研究     

HPLC-MS/ESI+测定人血浆中喹硫平及其代谢产物

目的建立同时测定人血浆中喹硫平及其磺氧化-、7-羟基-和7-羟基-氮-去烷基-代谢产物浓度的高效液相色谱-电喷雾电离质谱联用法.方法采用Kromasil C18 反相柱(250 mm×4.6 mm,5 μm),以水(含甲酸1.70 mmol·L-1, 醋酸铵5.8 mmol·L-1)-乙腈(6535)为流动相,流速0.95 mL·min-1. 质谱采用电喷雾电离源正离子模式(ESI+),选择离子监测(SIR)各物质准分子离子峰,样品用固相萃取法处理.结果喹硫平和磺氧化喹硫平在10～2 000 μg·L-1,7-羟基-喹硫平和7-羟基-氮-去烷基喹硫平在1～200 μg·L-1线性关系良好,萃取回收率均＞85%,方法回收率均＞95%,日内、日间RSD均＜15%.结论该方法专一性强、灵敏度高、简单,可用于研究喹硫平的代谢机制以及药物动力学.     

HPCE同时测定黄强软膏中盐酸小檗碱和泼尼松的含量

目的建立简便、快速的同时测定黄强软膏中盐酸小檗碱和泼尼松含量的高效毛细管电泳。方法以未涂层弹性石英毛细管(41 cm×50 μm,有效分离长度33 cm)为分离通道,30 mmol·L-1四硼酸钠(pH 11. 0)-甲醇(7∶3)为运行缓冲溶液,进样时间10 s,运行电压15 kV。紫外检测波长为238 nm。结果盐酸小檗碱在32.0～512 μg·mL-1内线性关系良好(r=0.999 9),平均回收率为99. 4%,RSD为1. 2%;泼尼松在16.0～256 μg·mL-1内线性关系良好(r=0.999 0),平均回收率为99. 8%,RSD为1. 4%。结论本法简便、快速,准确,为黄强软膏的质量控制提供了新的检测手段。     

LC-MS/MS测定人血浆中阿米舒必利的浓度

目的 建立测定人血浆中阿米舒必利浓度的高效液相色谱串联质谱电喷雾检测法(LC-MS/MS)。方法 以Welch Materials XB-C18(2.1 mm×150 mm,3 μm)为色谱柱,流动相为甲醇-水(95∶5,含5 mmol·L-1甲酸铵),流速为0.3 mL·min-1,柱温：40 ℃,以乙酸乙酯-二氯甲烷(4∶1)为提取溶剂。样品经电喷雾离子源正离子化后,通过三重四级杆串联质谱仪,采用选择反应监测(SRM)对阿米舒必利(m/z370.3→242.1)和内标舒必利(m/z324.2→112.1)进行测定。结果 阿米舒必利高(400 μg·L-1)、中(250 μg·L-1)、低(1.25 μg·L-1)3个浓度的平均方法回收率分别为104.44%、104.74%和95.65%,日内(n=5)、日间(n=3)RSD均小于15%;分析方法的最低定量限为0.52 μg·L-1。线性范围为：0.5～500 μg·L-1。结论 该方法灵敏、准确、简单、快速,可用于阿米舒必利临床血浓监测和药动学研究。     

单扫描极谱法测定天然麝香中的麝香酮

目的　建立天然麝香中麝香酮的含量测定方法。方法　样品用乙醇浸提 ,在 0 2 5g·L-1盐酸苯肼 - 1 0g·L-1氯化钠底液中 ,于峰电位 - 80 0mV(vs.SCE)处测定麝香酮。结果　麝香酮含量在 2 5～ 2 0 μg范围内线性关系良好 ,r =0 9995 ,方法检出限为 1 5 μg ,日内精密度 RSD =6 4 % (n =5 ) ,日间精密度RSD =7 0 % (n =5 ) ,平均回收率为 89 7%。结论　该方法快捷、简便易行。可用于麝香酮的含量测定     

反相高效液相色谱法测定血浆中文拉法辛浓度

目的 :建立高效液相色谱法检测人血浆中文拉法辛浓度。方法 :血浆样品经石油醚 乙醚 (2∶1 )提取后 ,有机相再用50mmol·L- 1盐酸反萃取并浓缩进样。色谱柱为氰基柱 (2 50× 4.6mm ,5μm) ,乙腈 -0 .1mol·L- 1NH4 H2 PO4 (2 5∶75)为流动相 ,UV检测波长 2 2 9nm。结果 :文拉法辛血浆最低检测浓度 1 0 μg·L- 1,线性范围 2 5～ 80 0 μg·L- 1,萃取回收率 75.5%～79.3%,加样回收率 97.4%～ 1 0 1 .2 %,日内RSD 4.87%～ 6 .39%,日间RSD 7.55%～ 1 0 .80 %。结论 :该法准确可靠 ,已用于临床患者文拉法辛血药浓度测定。     

HPLC-电化学法测定人血浆中盐酸克仑特罗浓度

目的　应用HPLC -电化学法检测人血浆中盐酸克仑特罗含量。方法　采用内标法定量,使用NucleodurC18色谱柱,以磷酸二氢钾缓冲液-乙腈(7∶3,V/V ,pH 5 .0 )为流动相,检测器电位0 .80V(Ag/AgCl)。结果　该方法的线性范围1.5～12 0μg·L-1,回归方程Y =0 .75 3X +0 .0 11,r=0 .9993;最低检测浓度0 .0 15 μg·L-1;RSD 2 .6 %～4 .2 % ;平均回收率93.4 %。结论　该方法适合临床监测     

高效液相色谱法测定人体内氯苯那敏血药浓度及药动学

目的建立高效液相色谱法测定人血浆中马来酸氯苯那敏药物浓度,并研究马来酸氯苯那敏健康人体药动学.方法Agilent C18柱(4.6 mm×250mm,5 μm),流动相为乙腈-0.025 mol·L-1磷酸二氢铵溶液(pH 3.5)(2773),检测波长为200 nm.10名健康志愿者单剂量口服8 mg马来酸氯苯那敏片后,体内药时数据采用3P97程序统计方法处理.结果本实验条件下,血浆样品中氯苯那敏无杂质干扰,线性关系良好,所得回归方程为C=0.323 5A-0.703,r=0.999 2,线性范围为0.75～48.00μg·L-1,本方法最低定量浓度为0.75μg·L-1,高、中、低3浓度日内和日间的RSD＜15%,提取回收率大于75%,满足生物样品的测定要求.马来酸氯苯那敏健康人体药动学参数Cmax为(16.4±8.9)μg·L-1,tmax为(3.8±1.5)h,t1/2ke为(13.1±2.3)h,V/F为(871.7±187.3)L,AUC0-t为(181.5±52.3)μg·h·L-1,AUC0-∞为(208.2±60.1)μg·h·L-1.结论本法操作简便快速,定量准确可靠,适用于马来酸氯苯那敏片的人体药动学研究.     

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.     

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.