HPLC荧光检测法同时测定盐酸曲马多及其代谢物M1血药浓度

目的： 建立一种用高效液相色谱法同时测定盐酸曲马多（ＴＭＤ） 及其主要代谢物Ｍ１ 血药浓度的方法。方法： 以０－０３ ｍｏｌ·Ｌ－ １ 四硼酸钠缓冲液（ 含三乙胺０－５ ％ , 磷酸调ｐＨ４－０） － 甲醇（６８∶３２） 为流动相, 用ＯＤＳ 柱分析盐酸曲马多及其代谢物Ｍ１ 的血药浓度, 柱温５０ ℃, 阿替洛尔作内标, 荧光检测： 激发波长为２７５ ｎｍ , 发射波长为３０４ ｎｍ , 血样处理采用冷冻的二次液－ 液反萃法。结果： 本法中ＴＭＤ 与代谢物Ｍ１ 的线性范围分别为４－５ ～４４６ 和３－１ ～３１２ ｎｇ·ｍ Ｌ－ １ , 最低检测限分别为２ 和１－５ ｎｇ·ｍ Ｌ－ １ 。回收率均在９５ ％ ～１００－３ ％ 内。结论： 本法同时测定ＴＭＤ 及其代谢物Ｍ１的血药浓度简便易行, 灵敏度高, 准确可靠     

柱切换HPLC法测定人血浆中阿霉素浓度

本文采用ＨＰＬＣ柱切换技术建立了阿霉素（Ａｄｒｉａｍｉｃｉｎ）血药浓度的测定方法。以μ－ＢｏｎｄａｐａｋＣ_（１８）（３７～５０μｍ）为预处理柱（５０ｍｍ×５ｍｍＩＤ），磷酸缓冲液为预处理流动相，对样品进行自动净化处理。分析柱（１５０ｍｍ×５ｍｍＩＤ）固定相为ＹＷＧ－Ｃ１８，１０μｍ，流动相为甲醇－乙腈－磷酸缓冲液（４０：１０：５０，Ｖ／Ｖ）的混合溶液。荧光检测波长为λ_（ｅｘ）＝４９５ｎｍ，λ_（ｅｍ）＝５６０ｎｍ。血浆测定的线性范围为３～６８２ｎｇ／ｍｌ，ｒ＝０．９９９８，血浆中最低检测浓度为１ｎｇ／ｍｌ。方法的平均回收率为１０１．０％，日内及日间相对标准偏差均小于６％。     

高效液相色谱法测定α—羟基苯丁酸的含量

本文报导了反相高效液相色谱法测定依娜普利中α－羟基苯丁酸含量的方法。在ＯＤＳ柱上测定，流行相为甲醇－－５ｍＭ磷酸（６０：４０），在２１０ｎｍ波长处检测。线性范围５－１００μｇ／ｍｌ，样品回收率１００．２，结果较令人满意。     

人血浆中奥美拉唑高效液相色谱测定法及其药代动力学研究

建立人血浆中奥美拉唑的高效液相色谱测定法,以测定志愿者口服２种奥美拉唑制剂后的血药浓度,并对２种制剂的生物等效性进行评价。方法：血浆中加入内标尼美舒利后,以乙醚提取,进行高效液相色谱法检测。色谱柱为ＨｙｐｅｒｓｉｌＯＤＳ２２０ｃｍ＊４．６ｍｍ,５μｍ,流动相为甲醇－水－冰醋酸－三乙胺。     

高效液相色谱法测定壮骨关节丸中补骨脂素和异补骨脂素的含量

目的： 测定壮骨关节丸中补骨脂素、异补骨脂素的含量。方法： 高效液相色谱法, ＡｌｌｔｉｍａＣ１８ 分析柱（２５０ ｍ ｍ ×４－６ ｍ ｍ , ５ μｍ） , 流动相： 甲醇－ 水（５０∶５０） , 检测波长： ２４５ ｎｍ , 流速：１－０ ｍＬ·ｍｉｎ － １ , 柱温： ４０ ℃。结果： 补骨脂素在０－０７４ ８ ～０－５９８ ４ μｇ （ｒ ＝ ０－９９９ ９） 、异补骨脂素在０－０７５ ４ ～０－６０３ ２ μｇ （ｒ ＝ ０－９９９ ９） 范围内呈线性; 补骨脂素和异补骨脂素平均回收率分别为９８－２８ ％ （ ＲＳＤ＝ １－６ ％ ） 和９８－７２ ％ （ ＲＳＤ＝ ２－０ ％ ） 。结论： 本方法简便、快速, 准确。     

HPLC法测定甲地高辛及其片剂的含量

用高效液相色谱法测定甲地高辛及其片剂的含量。色谱柱用ＯＤＳ－Ｃ１８；流动相为乙腈－水（４０∶６０）；紫外检测波长２１８ｎｍ，采用内标法。甲地高辛浓度在５～４０μｍ／ｍｌ时，浓度与峰面积之比呈良好线性关系。用于片剂含量测定的回收率为９９．８６％，（ＲＳＤ＝１．８９％）。     

HPLC法测定人血浆中氧化苦参碱含量

目的：建立测定氧化苦参碱血药浓度的ＨＰＬＣ法。方法：血浆标本经碱化以氯仿一正丁醇（９８∶２）提取,吹干后以甲醇一正己烷（４∶１,氨水调ｐＨ至８）为流动相,经过Ｓｐｈｅｒｉｓｏｒｂ－ＳｉＯ２（５μｍ）柱分离后在紫外２２０ｎｍ处检测。结果：氧化苦参碱血浆浓度曲线范围１２～３６ｍｇ·Ｌ－１,最低检出限为０１ｍｇ·Ｌ－１（Ｓ／Ｎ＝２）。样品在１２～３６ｍｇ·Ｌ－１浓度时的平均回收率为９８３１％～１０９０％,日内和日间精密度的ＲＳＤ均小于４％。结论：此方法为氧化苦参碱的血药浓度测定及药代力动学研究提供了一种简便可行的方法。     

反相高效液相色谱法测定苯巴比妥血药浓度

目的：建立一种快速测定苯巴比妥血药浓度的方法。方法：采用反相高效液相色谱法,以卡巴西平为内标,测定苯巴比妥血药浓度,钯谱柱ｓｈｉｍａｄｚｕ ｓｈｉｍｐａｃｋＣＬＣ－Ｃ１８不锈钢柱,流动相为甲醇－水（６０：４０）,流速０．８ｍｌ／ｍｉｎ,检测波长２５４ｎｍ。结果：在５～４０ｕｇ／ｍｌ逍度范围内线性良好（ｒ＝０．９９９９）,最低检测限为１１．５７ｎｇ／ｍｌ高、中、低三种浓度的平均回收率分别为１００．２４％,１００．２８％,９９．４１％,ＲＳＤ分别为０．７％,２．７％,５．８％（ｎ＝９）。日内和日间平均ＲＳＤ分别为３．３％,５．２％,８．７％和７．３％。７．３％,９．２％（ｎ＝９）。结论：该方法准确、快速、简便,灵敏度高,重现性好,可作为苯巴比妥血药浓度监测的常规方法。     

单硝酸异山梨酯片的HPLC测定

单硝酸异山梨酯（１）为新一代异山梨酯类抗心绞痛药。１９８１年首先在西德上市,国内已有片剂和缓释胶囊剂产品。其含量测定有比色法［卫生部药品标准ＷＳ－１３０（Ｘ－１１０）－９４］、气相色谱法［１］（用于片剂）和ＨＰＬＣ法［２］（用于胶囊剂）。本文采用ＨＰＬＣ外标法测定其片剂含量,与比色法相比,本法简便、快速,结果准确。１　仪器与试药ＴＳＰ高效液相色谱仪（美国理光光学仪器公司）,包括ＵＶ－６０００ＬＰ型检测器。色谱柱：ＰｈｅｎｏｍｅｎｅｘＣ１８柱（２５０×４．６０ｍｍ,５μｍ）;流动相：甲醇－水（４０…     

高效液相色谱法测定司巴沙星片临床血药浓度

建立测定人血浆中司巴沙星药物浓度的ＲＰ－ＨＰＬＣ法,为临床合理用药提供必要的分析方法。方法：采用ＨＰＬＣ法,色谱柱为ＹＷＧ ＲＰ－Ｃ１８（１５０ｍｍ＊４．６ｍｍ,１０μｍ）;流动相为５０ｍｍｏｌ／ＬＮａＡｃ－ＨＡｃ缓冲液（ｐＨ５．０）;乙腈：甲醇＝７０：２０：１０（含０．０４％三乙胺,调ＰＨ２．４０）,检测波长２９９ｎｍ。血样（含内标对羟基苯乙酮）用７ｍｌ二氯甲烷一次提取,浓缩后取２０μｌ进样作Ｈ     

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.     

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.     

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.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.