美洛昔康胶囊人体生物等效性的研究

目的 评价美洛昔康胶囊(受试制剂)和美洛昔康片(参比制剂)在健康人体的生物等效性.方法 采用HPLC-UV法,测定人血浆中美洛昔康的浓度,并进行方法学验证;采用随机交叉自身前后对照试验设计,20名受试者分别口服受试制剂和参比制剂15 mg后,测定美洛昔康的血药浓度,计算药动学参数,评价两制剂的生物等效性.结果 美洛昔康胶囊和美洛昔康片的t1/2分别为24.61±10.46、26.56±7.57 h,Cmax分别为2.45±0.33、2.49±0.37 μg· mL-1,Tmax分别为4.58±1.35、5.05 ±1.51 h;AUC0→1分别为76.57±17.71、84.12±19.91 μg·h·mL-1.美洛昔康胶囊的相对生物利用度为92.8％±17.7％.结论 两制剂在健康中国人体内具有生物等效性.     

HPLC法测定美洛昔康血药浓度及其药动学

目的:建立测定美洛昔康血药浓度的HPLC法,并研究该药在人体内的药动学。方法:采用Waters公司色谱仪,Hypersil BDS C18色谱柱(250 mm×4.6mm,5μm),以甲醇-0.02 mol·L-1磷酸盐缓冲液(pH 5.2)-三乙胺(55:45:0.04,V/V)为流动相,检测波长360 nm。健康志愿者给美洛昔康15 mg后,测定血药浓度,绘制药-时曲线并计算药动学参数。结果:美洛昔康浓度在0.02-3.0 mg·L-1范围内呈良好的线性关系,低、中、高3个浓度的提取回收率均>80％,方法回收率均在100％左右;日内、日间RSD均<10％。美洛昔康的主要药动学参数为AUC0→96h(63.50±14.75)nag·h·L-1,cmax(1.62±0.30)mg·L-1,tamx(5.75±3.28)h,T1/2ke(24.23±5.33)h。结论:本法快捷、灵敏、准确、重复性好,适用于美洛昔康血药浓度的测定和药动学研究。     

高效液相色谱法测定阿魏酸血浆浓度

目的 建立测定血浆中阿魏酸浓度的高效液相色谱法。 方法 固定相为NucleosilC18柱 ,流动相为甲醇 -水 -冰乙酸 (35∶6 5∶0 1) ,流速 1 0ml·min-1,检测波长 32 0nm。以替硝唑为内标 ,血浆样品酸化后用乙酸乙酯提取。峰高比定量。 结果 标准曲线线性范围 0 5～ 16 0 μg·ml-1,γ =0 9995 ,阿魏酸平均回收率 96 9%～ 10 0 6 % ,最低检测浓度 0 2 μg·ml-1,日内RSD <3 0 % ,日间RSD <5 4%。 结论 本方法简便 ,快速 ,准确 ,重现性好 ,适用于阿魏酸血药浓度测定及药代动力学研究     

HPLC测定人血浆中的酮洛芬

目的　建立人血浆中酮洛芬的HPLC测定法。方法　内标为布洛芬 ,用甲醇直接沉淀人血浆中蛋白质 ,上清液在HypersilBDSC18色谱柱上 ,以甲醇 -水 (6 0∶4 0 ,冰醋酸调pH 4 .0 )为流动相进行分离 ,流速 1ml·min-1,在UV2 5 7nm处检测。结果　酮洛芬和内标分离完全且无其他干扰 ,保留时间分别为 7.4 13、9.4 0 7min。线性范围为 0 .15～ 2 0 μg·ml-1,r =0 .9999,日内RSD为 1.0 8%～ 6 .0 1% ,日间RSD 1.11%～ 3.0 3% ,回收率为 97.4 %～ 10 5 .0 % ,血浆中酮洛芬的最低检测浓度为 0 .0 5 μg·ml-1。结论　所用方法简便、准确、重复性好 ,可用于口服酮洛芬缓释片后的血药浓度检测。     

美洛昔康RP-HPLC测定方法研究

目的建立血浆中美洛昔康浓度RP-HPLC分析方法,并对其在人体内的药代动力学过程进行研究.方法采用Supelco ODS色谱柱(4.6×250 mm,5mm),流动相为甲醇-pH 7.4磷酸盐缓冲液(11,V/V),流速1.0 m1·min-1,检测波长362 nm.结果美洛昔康在0.05～3 mg·L-1血浆浓度范围内线性关系良好(r=0.9978,n=5),最低检测浓度为0.05mg·L-1.0.1、1.0和2.0mg·L-1三种浓度的日内、日间RSD(n＝5)分别为10.71%、9.09%、8.12%和13.96%、11.44%、9.86%;绝对回收率平均(RSD)为80.57%.结论本实验建立的美洛昔康HPLC测定方法操作方便,结果准确,可用于该药进一步的临床药动学研究.     

离子对高效液相色谱法测定美洛昔康含量及有关物质

目的 :为控制美洛昔康的含量和有关物质 ,建立了离子对高效液相色谱测定法。方法 :色谱柱为Alltech公司AlltimaODS柱 (2 5 0mm× 4 6mm) ,流动相 :乙腈 -含 0 2 5 %辛烷磺酸钠的 0 1mol·L- 1 磷酸二氢钠 (磷酸调至pH 2 5 ) (6 5∶35 ) ,流速 :1mL·min- 1 ,检测波长分别为 35 5nm (含量测定 )和 2 71nm (有关物质测定 )。结果 :美洛昔康在 9～ 110 μg·mL- 1 范围内呈良好的线性关系 ,r=0 9998。结论 :本文改进的离子对高效液相色谱法为测定美洛昔康及其制剂的含量和有关物质提供了可靠基础。     

高效液相色谱法测定依托度酸及其在大鼠的药动学(英文)

目的 :建立测定依托度酸浓度的高效液相色谱法并研究该药在大鼠体内的药动学。方法 :血浆 2 0 0 μL加入 1 0 0mg·L-1 内标 (奥沙普秦) 50 μL ,酸化后用乙酸乙酯∶正己烷 (1∶1 9)提取。采用C1 8分析柱 ,以乙腈∶水∶三乙胺 (1 6∶84∶0 .0 0 2 )为流动相 ,流速为 1 .0mL·min-1 ;检测波长 2 80nm。大鼠按依托度酸 2 0mg·kg-1 剂量灌胃 ,给药前及给药后 5 ,1 0 ,2 0 ,30min和 1 ,3,6 ,1 2 ,2 4 ,48,72h采血 ,测定血浆药物浓度。绘制血药浓度 -时间曲线图并计算主要药动学参数。结果 :依托度酸与内标物的保留时间分别为 5 .2 8min和 6 .80min ;依托度酸浓度在1 .0～ 1 0 0 .0mg·L-1 范围内与依托度酸/内标物的峰面积比呈良好线性关系 ,回归方程为 :Y =0 .0 32 2 7C +0 .0 0 1 2 8,r =0 .9999,n =7。本法高、中、低浓度的绝对回收率为 73 .4 %～ 80 .5 % ,方法回收率在 97.3%～1 0 6.0 % ,日内RSD <4% ,日间RSD <8%。依托度酸的药动学参数为Tmax=0 .2 8h± 0 .1 3h ;Cmax=69mg·L-1 ± 5mg·L-1 ;T1 /2 =1 6 .9h± 2 .1h ;AUC =2 31 4mg·h·L-1 ±32 8mg·h·L-1 。结论 :本法快捷、灵敏、准确、重复性好 ,适用于依托度酸血药浓度测定及药动学研究。     

异福片的药物动力学与相对生物利用度

目的　研究两种异福片的药物动力学 ,并评价两者的生物等效性。方法　采用RP -HPLC测定 2 4名志愿受试者单剂量po异福片供试品与参比品后利福平和异烟肼血药浓度的变化 ,用 3p97药动学程序拟合药动学参数。结果　两种制剂中利福平AUC0→t分别是 16 3 6 6± 11.33μg·h·ml-1与 172 5 9± 76 .31μg·h ml-1,Tmax分别为 1.92± 0 .19h与 1.96± 0 .4 5h ,Cmax分别是 2 6 .4 2± 11.97μg·ml-1与 2 6 .18± 11.5 7μg·ml-1。两种制剂中异烟肼AUC0→t分别是 4 4 .2 6± 18.84 μg·h·ml-1与 4 6 .18± 16 .6 0μg·h·ml-1,Tmax分别为 1.83± 0 .33h和 1.88± 0 .31h ,Cmax分别是 7.73± 3.2 2 μg·ml-1与 7.76± 3.0 0 μg·ml-1。经剂量校正 ,两种制剂中两组份的lnAUC0→∞ 、lnAUC0→t、Cmax经方差分析均无显著性差异 (P >0 .0 5 ) ;Tmax用双单侧t检验进行生物等效性评价 ,无显著性差异 (P >0 .0 5 )。结论　两种制剂为生物等效制剂 ,异福片供试品中利福平和异烟肼的相对生物利用度分别为95 .86 %± 11.86 %和 95 .5 4 %± 12 .5 3%。     

LC-MS/MS法测定大鼠血浆伏立康唑、伏立康唑氮-氧化物浓度及药动学应用研究

摘要：目的:建立液相色谱-串联质谱（LC-MS/MS）法测定大鼠血浆中伏立康唑及伏立康唑氮-氧化物浓度,并探索灌胃给予伏立康唑后两者在大鼠体内的药动学过程。方法:样品预处理选用甲基叔丁基醚作萃取剂,通过液-液萃取法消除基质效应。采用Welch Ultimate UHPLC XB-C18（50 mm×2.1 mm; 1.8μm）色谱柱;以乙腈-水(含2 mmol·L-1甲酸铵,0.1%甲酸)为流动相进行梯度洗脱;柱温：35℃;流速：0.35 ml·min-1;分析时长：4 min;质谱方法应用电喷雾离子源,多反应监测模式进行正离子检测。利用该方法分别测定大鼠灌胃给予66.7 mg·kg-1伏立康唑后各时间点伏立康唑及伏立康唑氮-氧化物的血药浓度,分析其在大鼠体内的药动学过程。结果:伏立康唑及伏立康唑氮-氧化物在0.5～500 ng·ml-1范围内线性关系良好（r＞0.999 0）,定量下限均为0.5 ng·ml-1。用建立的方法测定伏立康唑及伏立康唑氮-氧化物血药浓度,拟合得到其药动学参数：药时曲线下面积（AUC）0-t分别为（54.66±20.30）μg·ml-1·h,（10.88±5.30）μg·ml-1·h;AUC0-∞分别为（54.66±20.30）μg·ml-1·h,（13.50±2.10）μg·ml-1·h;清除率（CL）分别为（4.19±0.90）L·min-1·kg-1,（18.98±3.70）L·min-1·kg-1;药峰浓度(Cmax)分别为（19.14±11.90）μg·ml-1,（0.95±0.20）μg·ml-1;半衰期(t1/2)分别为（5.89±6.10）h,（6.11±3.20）h。结论:该方法快速、简便、准确度高且重复性好,可用于伏立康唑及伏立康唑氮-氧化代谢产物在大鼠体内的药动学研究。     

高效液相色谱法测定异丁司特的血药浓度

目的 :建立高效液相色谱法测定人血浆中异丁司特浓度的方法。方法 :采用YWG C18色谱柱 ,以甲醇 0 .0 5mol·L-1磷酸二氢钾 (6 5∶35 ,用磷酸调pH值 3.5 )为流动相 ,检测波长 2 2 5nm ,流速 1.0mL·min-1,进样量 5 0 μL ,内标物为桂利嗪。 结果 :异丁司特标准曲线在 2～ 12 0 μg·L-1范围内线性关系良好 (r =0 .995 6 ) ,最低检测浓度为 2 μg·L-1,平均回收率为10 0 .2 % ,RSD为 4 .7% (n =5 )。结论 :该法操作简便 ,灵敏 ,准确度高 ,适用于异丁司特血药浓度的测定和药动学的研究。     

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.     

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.     

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.     

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.