高效液相色谱法测定人血清中盐酸马普替林的浓度

本文建立了反相高效液相色谱法测定人血清中马普替林浓度的方法。本法用ＺｏｒｂａｘＯＤＳＣ１８色谱柱，以甲醇－水－氨水（５ｍｏｌ／Ｌ）－１０％醋酸铵＝４００∶７５∶１０∶１为流动相，检测波长为２５４ｎｍ，流速０．８ｍｌ／ｍｉｎ，线性范围２０～２４００ｎｇ／ｍｌ（ｒ＝０．９９９７），平均回收率为９８．０％±３．９％，日内与日间的标准差分别为３．２％和４．９％     

高效液相色谱法测定人血清中伊曲康唑浓度

目的：建立了ＨＰＬＣ法测定血清样品中伊曲康唑的定量分析方法。方法：色谱条件：以ＺＯＲＢＡＸＴＭＣ１８（５μｍ,４．６×１５０ｍｍ）为色谱柱;乙腈水（６７．５∶３２．５）为流动相,检测波长２６３ｎｍ;用正庚烷∶异戊醇（９８．５∶１．５）作为提取剂。结果：三种浓度４０,８０,３００ｎｇ·ｍｌ－１回收率分别为１０５．０５％,１００．５７％,９７．９１％（ｎ＝６）;日内、日间ＲＳＤ分别为３．８３％,４．０５％,３．０９％及６．００％,４．９０％,４．７２％（ｎ＝６）。血清中药物的最低检测浓度为５ｎｇ·ｍｌ－１,在５～６００ｎｇ·ｍｌ－１血药浓度范围内线性关系良好,ｒ＝０．９９９５。结论：方法灵敏、准确、结果满意     

硫酸长春地辛及其注射剂含量测定方法的改进

采用反相高效液相色谱法，改进了硫酸长春地辛及其注射剂含量测定条件。以Ｃ１８柱（１５０ｍｍ×４．６ｍｍ），甲醇－１．５％二乙胺（７０３０，磷酸调节ｐＨ至７．５）为流动相，测得原料药及注射剂的平均回收率分别为９９．９８％和９９．８０％，ＲＳＤ分别为０．１９％和１．５％。结果准确、稳定     

高效液相色谱法测定复方咪康唑霜中咪康唑和培氯米松的含量

采用高效液相色谱法，以益康唑为内标，在Ｎｏｖａ－ＰａｋＣ１８柱上，甲醇－水（含０．０５％二乙胺）为流动相，分离测定了复方咪康唑霜中咪康唑和培氯米松的含量。方法简便，灵敏且峰形好。硝酸咪康唑的回收率为９８．３％（ＲＳＤ＝１．１％，ｎ＝５）；丙酸培氯米松的回收率为９７．６％（ＲＳＤ＝１．４％，ｎ＝５）。     

反相高效液相色谱法测定西替利嗪血药浓度及其在药动学研究中的应用

目的：建立测定西替利嗪在人体血浆中浓度的反相离子对高效液相色谱法（ＲＰ－ＨＰＬＣ）。方法：以Ｎｏｖａ－ＰａｋＣ１８４μｍ色谱柱为分离柱，流动相为乙腈∶磷酸盐缓冲液（０．０２ｍｏｌ·Ｌ－１ＮａＨ２ＰＯ４）∶三乙胺（５０∶５０∶０．１５，ｐＨ３．１５，内含十二烷基硫酸钠（ＳＤＳ）０．００９５ｍｏｌ·Ｌ－１，普萘洛尔为内标，ＵＶ检测波长２２９ｎｍ。结果：方法线性范围１０～４００ｎｇ·ｍｌ－１（ｒ＝０．９９９８），平均回收率为９８．１％±０．８％，日内和日间精密度均小于３％。结论：应用本法研究西替利嗪片剂在正常人体内的药动学，具有简便、迅速、准确之特点     

二乙基二硫代氨基甲酸钠抑制顺铂的致突变作用

二乙基二硫代氨基甲酸钠（ＤＤＴＣ）能明显抑制顺铂诱导鼠伤寒沙门氏菌ＴＡ１００，ＴＡ９８回变，有Ｓ９代谢活化系统时抑制作用增强，１６０．７４μｇ／ｐｌａｔｅＤＤＴＣ对０．２５～２．００μｇ／ｐｌａｔｅ顺铂抑制率为８７．４％～９５．７％（ＴＡ１００）和８９．４％～１０５．５％（ＴＡ９８）．小鼠ｉｐ顺铂１．５ｍｇ·ｋｇ－１，２４ｈ重复ｉｐ１次，每次给顺铂后１ｈｉｐＤＤＴＣ４００～８００ｍｇ·ｋｇ－１或同时ｉｇＤＤＴＣ７５０～１５００ｍｇ·ｋｇ－１．可显著降低顺铂诱发小鼠骨髓多染红细胞微核的形成．体内外实验结果表明ＤＤＴＣ可降低顺铂的致突变作用     

高效液相色谱法测定人体地尔硫及其主要代谢物的药物动力学

用高效液相色谱法（ＨＰＬＣ）测定人血清中地尔硫（ＤＺ）及去乙酰地尔硫（Ｍ１）浓度。以ＳｐｈｅｒｉｓｏｒｂＯＤＳ，５μｍ为层析柱，流动相：甲醇∶乙腈∶水（６０∶１０∶３０），检测波长２３７ｎｍ，以盐酸普罗帕酮为内标。检测范围：ＤＺ为５．４５～２７２．５ｎｇ·ｍｌ－１，Ｍ１为５．８５～２９２．５ｎｇ·ｍｌ－１。最低检测浓度：ＤＺ为２．８７ｎｇ·ｍｌ－１，Ｍ１为１．９９ｎｇ·ｍｌ－１。平均回收率ＤＺ为１０１．８８％，Ｍ１为１０１．７２％，ＲＳＤ均在１２％以内。并对４名受试者口服９０ｍｇ盐酸地尔硫片后，其药时曲线经微机用ＰＫＢＰ－Ｎ１程序拟合，ＤＺ为一房室开放模型，Ｍ１为二房室开放模型，求得ＤＺ和Ｍ１的Ｔ１／２分别为５．６±１．５ｈ和１４±７ｈ。     

高效液相色谱法测定生物样品中两性霉素B

两性霉素Ｂ（ＡＭＢ）常用于内脏或全身真菌感染的治疗。由于ＡＭＢ对肝、肾等有较大毒性，应监测血浆中ＡＭＢ的浓度，以便调整其用量。我们采用高效液相色谱法（ＨＰＬＣ），在μ－ＢｏｎｄａｐａｋＣ１８柱（３．９ｍｍ×３００ｍｍ，１０μｍ）上，以０．０５ｍｏｌ／ＬＥＤＴＡ－２Ｎａ溶液－乙腈（１∶１）为流动相；流速为１．４ｍｌ／ｍｉｎ；检测波长为４０５ｎｍ，测定了血浆、脑脊液中ＡＭＢ浓度。ＡＭＢ血浆中最小检出量为０．０２μｇ／ｍｌ。血浆中ＡＭＢ提取率＞８７％。日内精密度在５．０１％～６．２８％之间，日间精密度血样＜７．８６％，ＣＳＦ＜５．９８％。血浆中ＡＭＢ浓度在０．０５～２．０μｇ／ｍｌ范围内有良好线性关系。方法回收率为９９．０４％±３．９０％。该法用于１例曲霉菌全身感染者ＡＭＢ血药浓度测定，为制定给药方案提供了依据。     

熊脱氧胆酸的毛细管气相色谱法测定

改进了熊脱氧胆酸（１）的羧基甲酯化和羟基乙酰化的衍生化条件。ＣＧＣ采用ＯＶ－１柱，氢气作载气，２６０℃（保持５ｍｉｎ）～２８０℃程序升温，升温速率为４℃／ｍｉｎ，ＦＩＤ检测。１在６．０～１４．０μｇ线性良好，＝０．９９７７；１在熊胆粉和栓剂中的平均回收率分别为９８．１％（ＲＳＤ＝２．３％）和１００．３％（ＲＳＤ＝２．６％）。     

高效液相色谱法测定西替利嗪尿药浓度

目的：建立测定西替利嗪尿药浓度的反相离子对高效液相色谱法（ＲＰ－ＨＰＬＣ）。方法：以Ｎｏｖａ－ｐａｋＣ１８、４μｍ色谱柱为分离柱，流动相为乙腈∶磷酸盐缓冲液（０．０２ｍｏｌ·Ｌ－１、ＮａＨ２ＰＯ４）∶三乙胺（５０∶５０∶０．１５，Ｖ／Ｖ），ｐＨ值３．０７，内含十二烷基硫酸钠（ＳＤＳ）０．０１０５ｍｏｌ·Ｌ－１，去氯羟嗪为内标，ＵＶ检测波长２２９ｎｍ。结果：方法线性范围为０．２～２０μｇ·ｍｌ－１（ｒ＝０．９９９９），平均回收率为９６．４％±２．３％，日内和日间精密度均小于５％。结论：采用ＲＰ－ＨＰＬＣ法测定盐酸西替利嗪片的正常人尿药浓度，简便，迅速，准确     

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.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

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.     

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.