HPLC法测定维生素E烟酸酯血浓度及药代动力学研究

目的:建立人血浆中维生素 E 烟酸酯的 HPLC 测定方法,进行维生素 E 烟酸酯的人体药代动力学研究。方法:20名健康志愿者口服维生素 E 烟酸酯颗粒剂400 mg,取血浆经预处理后采用 HPLC 法测定维生素 E 烟酸酯经时血浓度,固定相为Phenomenex Luna C_(18)色谱柱(150 mm×4.6 mm,5 μm),流动相为甲醇-乙腈(85:15),流速1.0 mL·min~(-1),检测波长264 nm,DAS 2.0软件计算相应药代动力学参数。结果:维生素 E 烟酸酯在0.025～1μg·mL~(-1)范围内线性关系良好,日内、日间精密度均小于10%。健康志愿者维生素 E 烟酸酯主要药代动力学参数为:t_(1/2)=(6.52±2.16)h,T_(max)=(4.40±0.31)h,C_(max)=(0.46±0.08)μg·mL~(-1),AUC_(0-24)=(2.50±0.39)μg·mL~(-1)·h,AUC_(0-∞)=(2.74±0.42)μg·mL~(-1)·h,MRT_(0～24)=(8.35±0.44)h,CL/F=(2.31±0.43)L·h~(-1)·kg~(-1),V/F=(21.46±7.12)L·kg~(-1)。结论:本方法简单,灵敏度、专属性好。维生素E烟酸酯人体药代动力学过程符合二室模型,表观分布容积大,体内平均滞留时间长。     

HPLC法测定注射用12种复合维生素中维生素D_2、维生素A与维生素E的含量

目的:建立以高效液相色谱法同时测定注射用12种复合维生素中维生素D2、维生素A与维生素E含量的方法。方法:色谱柱为Inertsil(ODS-2)C18,流动相为乙腈-甲醇-二氯甲烷(80∶10∶10) ,流速为1mL·min-1,检测波长为265nm,进样量为10μL,柱温为30℃。结果:维生素D2、维生素E醋酸酯与维生素A棕榈酸酯检测浓度的线性范围分别为0.61～1.43、222.6～519.4μg·mL-1和1.21～2.82mg·mL-1;平均回收率分别为99.79%、99.53%、101.63%,RSD分别为1.667%、0.184 6%、0.113 4%。结论:本方法简单、快速、准确,可用于复合维生素制剂的含量测定。     

维生素E烟酸酯胶囊在健康志愿者的生物等效性

目的研究维生素E烟酸酯胶囊(抗氧化剂)在健康志愿者体内的相对生物利用度并评价其生物等效性。方法采用双周期随机交叉给药方法,22名健康男性志愿者分别单剂量口服试验和参比的维生素E烟酸酯胶囊0.2g。用HPLC-MS法测定血浆药物浓度,计算2者的药代动力学参数及相对生物利用度,经统计分析进行生物等效性判定。结果单剂量口服维生素E烟酸酯胶囊试验制剂和参比制剂0.2g后,主要药代动力学参数:Cmax分别为(413.8±245.5)、(383.1±164.9)ng.mL-1;tmax分别为(5.09±0.43)、(5.23±0.61)h;AUC0-48分别为(1641.5±1042.6)、(1654.9±772.3)ng.h.mL-1;AUC0-∞分别为(1654.2±1055.9)、(1672.6±790.8)ng.h.mL-1。试验制剂的相对生物利用度为(99.41±34.62)%。结论2种维生素E烟酸酯制剂具有生物等效性。     

聚乙二醇1000维生素E琥珀酸酯中单双酯的制备及5种成分含量测定

目的 分离制备聚乙二醇1000维生素E琥珀酸酯中的单酯与双酯,并采用HPLC-UV、HPLC-ELSD测定聚乙二醇1000维生素E琥珀酸酯中的单酯、双酯、维生素E琥珀酸酯、α-生育酚及聚乙二醇1000的含量。方法 制备液相色谱分离采用DAC-HB50 C₁₈动态轴向压缩色谱柱（50 mm×250 mm,10 μm）,以水（A）-乙醇（B）为流动相,梯度洗脱,流速75 mL·min^-1,检测波长285 nm,收集目标组分旋蒸去除溶剂制得单酯、双酯,并确证其结构。含量测定色谱条件：Waters XBridge C₈色谱柱（4.6 mm×250 mm,5 μm）,0.1%甲酸溶液为流动相A,乙腈-异丙醇（1∶1）为流动相B,梯度洗脱,流速1.0 mL·min^-1,检测波长285 nm。HPLC测定制得的单双酯纯度及单酯、双酯、维生素E琥珀酸酯、α-生育酚含量;HPLC-ELSD测定聚乙二醇1000含量,采用相同色谱柱与流动相,进行不同的梯度洗脱,ELSD漂移管温度90.4℃,载气流速2.3 L·min^-1。结果 制得单、双酯纯度分别为99.1%,99.8%。各成分分离良好,在相应的范围内线性关系良好,相关系数r≥0.999 5;平均回收率为98.2%~99.7%。结论 制备液相色谱法可制得满足检测需求的单、双酯对照品;2种检测方法经验证,适用于聚乙二醇1000维生素E琥珀酸酯中单酯、双酯、维生素E琥珀酸酯、α-生育酚及聚乙二醇1000的含量测定。     

HPLC测定注射用脂溶性维生素中4种成分的含量

目的 建立高效液相色谱法同时测定注射用脂溶性维生素中维生素A棕榈酸酯、维生素D2、E、K1含量的方法。方法 采用Intersil (ODS-2) C18 (150 mm×4.6 mm,5 μm)色谱柱,以甲醇-乙腈-乙醇-水(20∶55∶25∶6)为流动相,流速1.5 mL·min-1,检测波长265 nm。 结果 维生素A棕榈酸酯、维生素D2、E、K1进样量分别在1.19～2.78 μg、6.14～14.33 ng、10.92～25.48 μg、0.19～0.44 μg内呈良好的线性关系;平均回收率分别为99.70%(RSD=0.48%)、100.13%(RSD=0.88%)、99.74%(RSD=0.69%)、99.97%( RSD=0.59%)。结论 方法操作简便、精确、结果可靠,可控制注射用脂溶性维生素的质量。     

HPLC法测定烟酸姜黄素酯及其纳米粒的含量

摘 要 目的：建立HPLC法测定烟酸姜黄素酯原料及其纳米粒中烟酸姜黄素酯的含量并进行方法学考察,为制剂工艺研究提供依据。方法: 采用C18色谱柱（250 mm×4.6 mm,5 μm）,流动相为乙腈 0.5％醋酸溶液（65∶35）、流速：1.0 ml·min^-1;检测波长:280 nm;柱温：30℃。结果: 烟酸姜黄素酯在5.200～104.000 μg·mL^-1范围内线性关系良好,r=0.999 4。烟酸姜黄素酯纳米粒及原料平均回收率分别为100.1％,100.9％,RSD分别为1.260％,0.995 0％（n=6）。结论: 该分析方法简单,准确,重复性好,可用于烟酸姜黄素酯纳米粒及原料中烟酸姜黄素酯的含量测定及制备工艺研究。     

维生素E烟酸酯对冠心病心率变异的影响

目的 :观察维生素 E烟酸酯对提高冠心病心率变异的效果。方法 :随机选择 2 6 8例冠心病 (CHD)患者。经过2 8d的维生素 E烟酸酯 0 .6 g/ d的治疗。测定治疗前后心率变异 (HRV)标准差。结果 :用药 2 8d后 ,治疗组与对照组标准差存在显著性差异 (P<0 .0 0 1)。结论 :维生素 E烟酸酯可提高 CHD患者 HRV,从而减少 CHD患者的猝死率     

双波长紫外分光光度法测定肝素钠肌醇烟酸酯乳膏中肌醇烟酸酯的含量

摘 要 目的： 建立肝素钠肌醇烟酸酯乳膏中肌醇烟酸酯的含量测定方法。方法: 采用双波长紫外分光光度法测定肌醇烟酸酯的含量。以262 nm为测定波长,246 nm为参比波长,ΔA ＝A₂₆₂－A₂₄₆为定量信息测定肌醇烟酸酯的含量。结果: 建立的肌醇烟酸酯含量测定方法可有效地消除基质对主药含量测定的干扰。肌醇烟酸酯在4~24 μg·ml^-1浓度范围内与吸光度差值ΔA线性关系良好,r=0.999 9;低、中、高浓度的平均回收率为99.11%,RSD为1.70%(n=9)。结论: 该方法操作简便快捷,稳定性好,结果准确,可用于肝素钠肌醇烟酸酯乳膏中肌醇烟酸酯的含量测定,有效控制该制剂的质量。     

紫外分光光度法测定维生素E烟酸酯胶囊的含量

本文采用紫外分光光度法测定维生素E烟酸酯胶囊的含量,线性范围:30～70ug/ml,r=0.9999,回收率:100.33±0.20%,与省标方法比较,结果基本一致.     

阿莫西林—舒巴坦匹酯片含量及有关物质质控分析方法的建立

目的:测定阿莫西林-舒巴坦匹酯片的含量及有关物质。方法:反相离子对高效液相色谱法。色谱条件:ODS柱,流动相为0.01mol·L~(-1)SDS(pH 2.5)-甲醇(45:55),流速为1.0mL·min~(-1),检测波长230nm。结果:舒巴坦匹酯和阿莫西林的线性范围分别为11.0～0.125mg·mL~(-1)和0.25～0.015 mg·mL~(-1),回收率分别为98.9％和98.5％,RSD分别为1.5％和1.6％(n=5)。阿莫西林和舒巴坦匹酯的相对吸收系数比为19.6。结论:该方法能简单、快速、准确地同时测定阿莫西林和舒巴坦匹酯的含量和有关物质。     

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.