高效液相色谱法测定人血浆中阿克他利的浓度及其药动学研究

目的 建立人血浆中阿克他利浓度的高效液相色谱检测方法。 方法 血浆样品采用液-液萃取的方法,采用Dikma C₁₈柱分离,以水(含1.2%乙酸)-甲醇 (50:50, V/V) 的混合溶液为流动相,检测波长为245 nm,流速为1.0 ml/min,柱温30 ℃。 结果 建立的人血浆内阿克他利测定方法线性范围为75~4 000 ng/ml,定量下限可达75 ng/ml。日内、日间精密度(RSD)均小于10%,方法准确度大于90%,提取回收率大于88%。 结论 该方法快速、灵敏、专属,适用于人血浆中阿克他利浓度的测定。     

高效液相色谱法测定壮骨颗粒中补骨脂素与异补骨脂素的含量

目的 建立高效液相色谱法测定壮骨颗粒中补骨脂素和异补骨脂素的含量。方法 色谱柱为Agilent Zorbax C₁₈柱（4.6 mm×250 mm,5 μm）,流动相为甲醇-水（45：55）,检测波长为245 nm,流速为1.0 ml/min,柱温为25 ℃,进样量为10 μl。采用70%乙醇水浴方法提取壮骨颗粒中的补骨脂素和异补骨脂素。结果 补骨脂素与异补骨脂素在3.75~40 μg/ml范围内呈良好的线性关系,对方法精密度（n=6）、重复性（n=6）和稳定性（12 h）进行考察,相对标准偏差（RSD）均小于2%。加样回收率（n=6）为94%~105%。结论 该测定方法简便、快速、准确,可用于壮骨颗粒的临床快速质量控制。     

高效液相色谱荧光法测定血浆中左氧氟沙星的浓度及其生物等效性研究

目的 建立高效液相色谱（HPLC）荧光法测定血浆中左氧氟沙星的浓度,研究盐酸左氧氟沙星片在健康人体中的生物等效性。方法 采用随机交叉自身对照试验设计,24名健康男性受试者单次口服0.2 g盐酸左氧氟沙星片受试制剂或参比制剂,分别于不同时间点采集肘静脉血,采用HPLC荧光法测定血浆中左氧氟沙星的药物浓度。利用DAS 2.0软件计算药动学参数,评价两制剂的生物等效性。结果 受试制剂与参比制剂的主要药动学参数t _1/2、t_max、ρ_max、AUC_0-36和 AUC_0-inf分别为（6.71±0.95）h和（6.60±1.00）h;（0.85±0.30）h 和（0.79±0.28）h ;（2 815.48±513.04）ng/ml和（3 185.59±674.29）ng/ml;（17 157.61±1 949.07）ng·h/ml和（17 425.06±2 447.80）ng·h/ml;（18 324.52±2 019.41）ng·h/ml和（18 540.41±2 523.08）ng·h/ml。两制剂主要药动学参数统计学分析无显著性差异。受试制剂与参比制剂 AUC_0-36、AUC_0-inf 和 ρ_max对数比值的 90%置信区间分别为95.2%~102.5%、96.1%~102.2%和82.8%~94.9%。结论 受试制剂与参比制剂具有生物等效性,为生物等效制剂。     

高效液相色谱法测定降脂护肝胶囊中葛根素的含量

目的 建立高效液相色谱法测定降脂护肝胶囊中葛根素的含量。方法 色谱柱为Waters Symmetry C₁₈柱（4.6 mm×250 mm,5 μm）,流动相为乙腈-1%甲酸（11：89）,检测波长250 nm,流速1.0 ml/min,柱温30 ℃,进样量10 μl。结果 葛根素在2~40 μg/ml范围内（r=0.999 8）呈良好的线性关系,精密度实验中RSD均小于2%,加样回收率在98%~103%。结论 该测定方法简便、准确,分离效果好,可用于降脂护肝胶囊的质量控制。     

HPLC法测定扶正平消胶囊中吴茱萸次碱的含量研究

目的 建立高效液相色谱法测定扶正平消胶囊中吴茱萸次碱含量的方法。方法 样品经乙醇提取,乙酸乙酯液-液萃取后测定,色谱柱为Agilent TC-C₁₈,流动相为乙腈-四氢呋喃甲酸水溶液（2%四氢呋喃+0.2%甲酸）,流速为1.0 ml/min,柱温为40℃,检测波长为240 nm。结果 吴茱萸次碱含量在1.18~118 μg/ml范围内线性关系良好,r=0.999 9;其中日内、日间精密度RSD均<2%,平均加样回收率为94.20%。结论 本法准确、专属性强、重复性好,可用于测定扶正平消胶囊中吴茱萸次碱的含量。     

应用高效液相色谱法测定猫人参中积雪草酸的含量

目的 建立猫人参药材中积雪草酸的含量测定方法。 方法 采用高效液相色谱法,色谱柱为Agilent HC-C₁₈柱(4.6 mm×250 mm,5.0 μm),流动相为乙腈(30 mmol/L)-醋酸铵水溶液(35:65),流速1.0 ml/min,柱温25 ℃,紫外检测波长210 nm,进样量25 μl,运行时间35 min。 结果 积雪草酸与周围干扰峰达到基线分离,线性范围25.3~506.0 μg/ml, r=0.999 6;日内及日间精密度均<3% (n=5),平均回收率为99.4%(RSD=1.9%, n=6),猫人参中积雪草酸的含量为0.751 mg/g。 结论 该法简便快捷、测定结果准确、实用性强,可用于猫人参药材中积雪草酸的含量测定。     

两种盐酸特拉唑嗪片的人体生物等效性研究

目的 评价单剂量口服国产和进口盐酸特拉唑嗪片的人体生物等效性。 方法 采用单中心、随机、开放、双周期交叉试验设计,21名受试者在不同周期分别空腹口服国产和进口盐酸特拉唑嗪片2 mg,于给药前0 h及给药后60 h内不同时间点采集静脉血4 ml,采用液-质联用(LC-MS/MS)法测定受试者血浆中特拉唑嗪的浓度。 结果 国产和进口盐酸特拉唑嗪片的t_1/2分别为(13.2±2.39)和(12.5±1.93) h;t_max分别为(1.01±0.83)和(1.08±0.69) h;C_max分别为(40.1±10.6)和(37.3±9.57) ng/ml;AUC_0-∞分别为(428±82.1)和(426±85.2) ng·h/ml。国产盐酸特拉唑嗪片的相对生物利用度为(101.2±14.7)%。国产与进口盐酸特拉唑嗪片AUC_0-t和C_max几何均值比的90%置信区间(CI)均落在80%~125%之间。 结论 国产和进口盐酸特拉唑嗪片具有生物等效性。     

高效液相色谱法测定新保肾片中芦荟大黄素、大黄酸、大黄素、大黄酚和大黄素甲醚的含量

目的 建立新保肾片中芦荟大黄素、大黄酸、大黄素、大黄酚和大黄素甲醚的含量测定方法,为生产质量提供保障。方法 采用高效液相色谱法测定,色谱柱为Lichrospher-C₁₈柱(250 mm ×4.6 mm,5 μm),流动相为甲醇:0.1%磷酸溶液(7030),流速为1.0 ml/min,柱温为35 ℃,检测波长为254 nm。结果 芦荟大黄素、大黄酸、大黄素、大黄酚和大黄素甲醚分别在2.30~18.4 μg/ml(r=1.0)、2.930~23.44 μg/ml(r=1.0)、5.00~40.0 μg/ml(r=1.0)、14.870~118.96 μg/ml (r=0.999 8)、7.410~59.28 μg/ml(r=0.999 9)范围内有良好的线性关系,平均回收率分别为100.16%、102.91%、99.76%、100.32%、100.44%,RSD分别为1.58%、1.27%、1.67%、1.33%、1.03%(n=9)。结论 该方法准确易行,便于质量控制。     

高效液相色谱法测定康得灵胶囊中黄芩苷的含量

目的 建立康得灵胶囊中黄芩苷的HPLC测定方法。方法 色谱柱为Agilent Tc-C₁₈色谱柱（4.6 mm×250 mm,5 μm）,柱温为30 ℃;流动相为乙腈-0.5‰磷酸溶液（26：74）,流速为1.0 ml/min,检测波长265 nm。结果 黄芩苷保留时间约为16 min。以峰面积（Y）对进样浓度（X, μg/ml）线性回归,得回归方程：Y=22 114.67 X－112 836.7,r=0.998 8,线性范围5.410~108.2 μg/ml。平均加样回收率为98.78%,RSD为0.74%。结论 本方法操作简便,测定结果准确可靠,可用于康得灵胶囊中黄芩苷的含量测定。     

高效液相色谱法测定气管炎颗粒中黄芩苷的含量

目的 建立高效液相色谱法测定气管炎颗粒中黄芩苷的含量。 方法 采用HPLC法,色谱柱:ZORBAX SB-C₁₈柱(4.6 mm×150 mm,5 μm),以甲醇-0.1%磷酸(47:53)为流动相,流速为1 ml/min,检测波长为280 nm。 结果 黄芩苷在6.63~210 μg/ml范围内呈良好线性关系(r=0.999 8,n=6),平均加样回收率为98.16%,RSD为1.89%。 结论 本法简便、灵敏、准确、重复性好,结果可靠,可有效地控制气管炎颗粒的质量。     

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.     

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.     

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.     

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.