HPLC法测定注射用阿奇霉素枸橼酸二氢钠的含量及有关物质

目的:建立注射用阿奇霉素枸橼酸二氢钠含量和有关物质的测定方法。方法:采用高效液相色谱法,并与该制剂标准采用的含量测定方法(抗生素微生物检定法)及有关物质检查方法(薄层色谱法)测定结果进行比较。色谱柱为资生堂C18MGⅡ柱,流动相为磷酸盐缓冲液(pH8.2)-乙腈(45:55,V/V),流速为1.0ml/min,检测波长为215nm,柱温为35℃。结果:阿奇霉素检测质量浓度线性范围为0.5～3.0mg/m(lr=0.9999),平均回收率为100.2%,RSD=0.7%(n=9)。本方法主药含量测定结果与原标准方法结果一致,有关物质检查方法优于原标准方法。结论:建立的方法简便、准确、专属性强、重复性好,可用于注射用阿奇霉素枸橼酸二氢钠含量及有关物质的测定。     

HPLC法测定注射用阿奇霉素磷酸二氢钠的含量及有关物质

目的建立一种高效液相色谱方法来测定注射用阿奇霉素磷酸二氢钠含量及有关物质。方法以Shiseido C18(4.6 mm×250 mm,5μm)色谱柱为分析柱,以磷酸盐缓冲液(0.05 mol·L-1磷酸氢二钾溶液,用20%磷酸溶液调节pH值至8.2)-乙腈(40∶60)为流动相,柱温30℃,检测波长为210 nm,流速为1.0 mL·mim-1。结果阿奇霉素在10⁵ 000μg·mL-1范围内浓度与峰面积呈良好线性关系,r=1.000 0,平均回收率为100.6%,RSD为0.99%(n=9)。结论本方法可快速、准确的测定注射用阿奇霉素磷酸二氢钠含量及有关物质的测定。     

高效液相色谱法测定利福霉素钠含量与有关物质

目的建立高效液相色谱法测定注射用利福霉素钠含量及其有关物质的方法。方法色谱柱AlltechAlltimaC18(250mm×4.6mm,5μm);柱温35℃;流动相甲醇∶乙腈∶0.075mol/L磷酸二氢钾溶液∶1.0mol/L柠檬酸溶液(33∶33∶31∶4);流速1.0ml/min;检测波长254nm;进样量10μl。结果利福霉素的线性范围为0.01mg/ml～4.50mg/ml,r=1.0000,日内RSD为0.2%,日间RSD为0.1%～0.2%,平均回收率为99.7%(n=9),最低检测限为5.4ng。结论本方法简便快速,专属性好,精密度高,准确可靠,可作为控制利福霉素钠与注射用利福霉素钠含量及其有关物质质量的分析方法。     

HPLC法分析注射用乳糖酸阿奇霉素的有关物质和含量

目的:建立一种能用于注射用乳糖酸阿奇霉素中有关物质和含量控制的HPLC方法。方法:采用CAPCELL PAK C18(MGⅡ)柱(150 mm×4.6 mm,5μm),柱温30℃,流动相为磷酸盐缓冲液(0.05 mol.L-1磷酸氢二钾溶液,磷酸调pH至8.4±0.1)-乙腈(45∶55),流速1.0 ml.min-1,检测波长210 nm。结果:有关物质与主成分阿奇霉素能达到基线分离;酸根对有关物质的测定无影响;阿奇霉素在0.469 0～1.407 0 mg.ml-1范围内线性关系良好(r=0.999 5),平均回收率98.6%(n=6),RSD为0.4%。结论:该法简便,准确,其他组分不干扰测定,可用于本品的质量控制。     

RP-HPLC法测定注射用阿奇霉素有关物质

目的建立注射用阿奇霉素有关物质的新检测方法。方法采用反相高效液相色谱法检测注射用阿奇霉素中有关物质。液相色谱条件为：以Shim-pack CLC-ODS不锈钢柱（250 mm×4.6 mm,5μm）为色谱柱,以0.05 mol·L^-1K2HPO4-乙腈（40∶60）为流动相,流速1.0 ml·min^-1,柱温40℃,检测波长215 nm。结果阿奇霉素有关物质的检测限度为2.5%,阿奇霉素主峰与杂质峰分离完全。结论本方法能简单、灵敏、准确地检测注射用阿奇霉素中的杂质,适用于其有关物质检查。     

阿奇霉素中相关物质的分离及其体外抗菌活性的测定

目的研究阿奇霉素中主要相关物质的体外抗菌活性。方法采用HPLC法分离和制备阿奇霉素中的相关物质,色谱条件:采用LunaC18(2)制备柱(10μm,10mm×250mm);流动相:甲醇—水(92∶8);流速:5ml/min;柱温:室温;检测波长为215nm,进样方式为自动进样。用抗生素微生物检定法测定其体外抗菌活性。结果从阿奇霉素原料中分离出四种相关物质,其相对含量分别为0.3%、0.5%、0.4%和2.6%;其体外抗菌活性测定表明四种相关物质的效价分别为59、155、34和965μg/mg。结论有关药厂有必要控制阿奇霉素中相关物质的含量。     

HPLC测定注射用尼莫地平的含量及有关物质

目的建立测定注射用尼莫地平含量及有关物质的方法。方法采用HPLC法,用DiamonsilTMC18柱(250 mm×4.6 mm,5μm),流动相为甲醇-水-乙醚(70∶30∶9),检测波长238 nm,柱温为室温;流速1.0 ml.min-1。结果尼莫地平在4.0~40.0μg.ml-1范围内,峰面积和浓度呈良好的线性关系(r=0.9998),最低检测限为0.376 ng,方法精密度RSD=0.35%(n=6),平均回收率为99.8%(n=9)。结论所建方法准确、灵敏、简便、快速,可用于注射用尼莫地平的含量及有关物质的测定。     

HPLC法电化学检测阿奇霉素片的有关物质

目的:建立以高效液相色谱法电化学检测阿奇霉素片中有关物质的方法。方法:色谱柱为Gamma ARP-1/P,流动相为0.014mol·L-1磷酸氢二钾/0.020mol·L-1氢氧化钠(用磷酸和氢氧化钠调pH至11)-乙腈(71∶29),流速为0.7mL·min-1,柱温为40℃,进样量为50μL,玻璃碳电极的检测电位为+900mV。结果:红霉素过氧化物、阿奇霉素脱氧化物、阿奇霉素杂质A和N脱甲基阿奇霉素进样量的线性范围分别为0.15~1.80(r=0.999)、0.09~1.08(r=0.999)、0.23~2.76(r=0.998)、0.30~3.60μg(r=0.998);平均回收率分别为98.9%(RSD=1.1%)、94.6%(RSD=5.4%)、103.4%(RSD=3.4%)、96.2%(RSD=4.3%),有关物质含量检测结果均<0.7%。结论:本方法重现性好、灵敏度高、结果稳定准确,可用于检测该制剂的有关物质。     

HPLC法分析阿奇霉素及各类注射剂中有关物质的含量

目的建立一种能用于阿奇霉素原料及制剂中有关物质控制的HPLC方法。方法采用XBridge Shield RP18柱(250mm×4.6mm,5μm),柱温30℃,流动相为乙腈∶pH8.2磷酸盐缓冲液(0.05mol/L磷酸氢二钾溶液,用20%磷酸调节pH至8.2)(55∶45),流速1.0ml/min;检测波长210nm;样品溶液的进样量为200μg。结果阿奇霉素与其杂质(氮杂红霉素A,红霉素A肟,N-去甲基阿奇霉素,阿奇霉素德糖胺以及阿奇霉素N-氧化物)能达到基线分离;盐酸、硫酸、乳糖酸、柠檬酸、马来酸等阿奇霉素注射剂中常用酸根对阿奇霉素有关物质的测定无影响;方法的线性、准确性、灵敏度以及粗放性均能满足要求。结论本文所建方法能较好地反映国产各种阿奇霉素原料及制剂中的有关物质的情况,为国内市场上不同阿奇霉素注射剂的评价、阿奇霉素及其口服制剂的质量控制提供了较好的分析手段。     

HPLC法测定门冬氨酸洛美沙星注射液的含量和有关物质方法研究

目的 :建立高效液相色谱 (HPL C)法测定门冬氨酸洛美沙星注射液的含量和有关物质。方法 :Diamonsil C1 8色谱柱 (2 5 0 mm× 4 .6 mm ,5μm) ,以乙腈 -磷酸盐缓冲液 - 0 .0 5 mol/ L四丁基溴化铵溶液 (19∶ 81∶ 4 )为流动相 ,流速为1.0 ml/ min,用外标法测定 ,检测波长为 2 88nm。结果 :在 16～ 14 4μg/ ml的浓度范围内 ,洛美沙星的浓度与色谱峰面积呈良好的线性关系 ,r=0 .9997;回收率为 99.9% ,RSD=1.2 % ;最低检测量为 2 ng/ ml。结论 :该法准确、简便、灵敏 ,可用于门冬氨酸洛美沙星注射液的含量测定和有关物质检查。     

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.