HPLC法测定福多司坦口服液的含量和有关物质

目的：建立高效液相色谱法测定福多司坦口服液的含量和有关物质.方法：色谱柱：Diamonsil C18（150 mm×4.6mm,5μm）,流动相：乙腈-水（含0.025 mol·L-1辛烷磺酸钠和0.01 mol·L-1磷酸氢二钠,磷酸调pH至2.15）（10：90）,流速：1.0 ml·min-1,柱温：室温,检测波长：210 nm.结果：福多司坦在5.00～500.10 μg·ml-1范围内线性关系良好（r=0.999 9,n=6）,平均回收率100.41%,RSD为0.84%（n=9）.结论：该方法可用于福多司坦口服液的含量测定和有关物质检查.     

高效液相色谱法测定福多司坦原料药的含量

目的建立福多司坦原料药含量的测定方法。方法采用高效液相色谱法,以十八烷基硅烷键合硅胶柱C18(250mm×4.6mm,5mm)为色谱柱,水-甲醇(99.5:0.5)为流动相,流速为0.8mL/min,检测波长:220nm,温度:30℃。结果福多司坦的线性范围为y=1575.2x-1319,r=0.989242,平均回收率为95.89%(RSD=1.7%)。结论该法精确可靠,简单方便,建立了HPLC法测定福多司坦原料药中的福多司坦含量的方法。     

荧光分光光度法测定福多司坦片剂的含量

目的建立一种灵敏、准确的荧光分光光度法用于测定福多司坦片的含量.方法以邻苯二甲醛为衍生剂,对福多司坦进行衍生化,在λex=342 nm、λem=454nm处测定荧光强度.结果福多司坦的线性范围为0.5～6μg·ml-1,r=0.9999.平均回收率为100.3%,RSD为0.5%(n=9).结论方法简便易行,灵敏度高,重复性好,可用于福多司坦片的含量测定.     

HPLC法测定福多司坦原料药及其制剂中有关物质的含量

目的:建立福多司坦原料药及其制剂中有关物质含量测定的方法。方法:以国内8家企业生产的福多司坦原料药或制剂为样品。采用高效液相色谱(HPLC)法(外标法)测定杂质A、B、C的含量,色谱柱为MGⅡC_(18),流动相为0.12%己烷磺酸钠溶液(pH 2.0),流速为1.0 mL/min,检测波长为210 nm,柱温为35℃,进样量为20μL。采用HPLC法(加校正因子的主成分自身对照法)测定杂质E、F、G的含量,色谱柱为Altech Altima C_(18),流动相为0.05 mol/L磷酸盐缓冲液-乙腈-水(梯度洗脱),流速为0.5mL/min,检测波长为200 nm,柱温为30℃,进样量为20μL。结果:杂质A、B、C、E、F、G的检测质量浓度线性范围分别为0.446～22.291、0.202～20.158、0.101～12.082、0.111 0～11.100、0.210 4～10.520、0.221 6～11.080μg/mL,检测限分别为5.57、1.01、1.99、2.22、4.21、4.43 ng,定量限分别为11.14、2.02、3.98、4.45、8.42、8.85 ng;杂质E、F、G的校正因子分别为0.91、1.42、1.73,相对保留时间分别为0.88、1.95、3.08;精密度(n=6)、稳定性[杂质A(4 h,n=3),其余各杂质(24 h,n=7)]试验的RSD均小于2.0%,平均加样回收率分别为98.0%、97.3%、102.4%、99.4%、98.9%、96.4%,RSD分别为1.4%、1.5%、1.1%、0.9%、1.2%、0.5%(n=9);8家福多司坦原料药或制剂生产企业中杂质总含量均<1.1%。结论:该方法灵敏度高、专属性好,可用于福多司坦原料药及其制剂中有关物质的定量研究。     

反相高效液相色谱法测定拉坦前列素滴眼液的含量

目的建立RP-HPLC测定拉坦前列素滴眼液含量的方法。方法采用Chiralcel OD-R色谱柱(4.6mm×250 mm,5μm),以0.025 mol·L-1磷酸盐缓冲液-乙腈(55:45)为流动相,检测波长为200 nm,流速0.5mL·min-1。结果拉坦前列素质量浓度在0.999⁸.991μg·mL-1与峰面积呈良好的线性关系(r=0.999 9,n=5);定量限为2.0 ng;平均回收率分别为102.2%、100.7%、101.9%;RSD分别为0.19%、0.31%、0.02%(n=3)。结论该方法灵敏度高,操作简便,可满足本品含量测定。     

反相高效液相色谱法测定福多司坦片的含量

目的建立以RP-HPLC法测定福多司坦片中福多司坦含量的方法。方法采用C8反相柱,流动相为0·2%磷酸氢二钾溶液-乙腈(90∶10),调节pH值至4·5,检测波长210nm。结果福多司坦在50·35~805·6μg·ml-1的浓度范围内,峰面积与浓度呈良好的线性关系(r=0·9998);本法的相对标准偏差RSD为0·54%,平均回收率为100·06%(n=9)。结论本法快速、准确,精密度良好,可用于福多司坦片的含量测定。     

高效液相色谱法测定头孢呋辛赖氨酸原料药的含量

目的:建立高效液相色谱法测定头孢呋辛赖氨酸原料药的含量。方法:采用Kromasil C8(250 mm×4.6 mm,5μm)色谱柱,流动相为pH 3.4,0.1 mol.L-1醋酸盐缓冲液-乙腈(85∶15),流速为1.0mL.min-1,柱温为35℃,检测波长为273 nm。结果:头孢呋辛在1.97～39.49μg.mL-1范围内,浓度与峰面积呈良好线性关系,相关系数r=0.999 8(n=7),平均回收率为99.6%(n=9,RSD=0.6%)。结论:本法操作简便,结果准确,可用于头孢呋辛赖氨酸原料药的含量测定。     

离子色谱法测定碳酸锂原料药中的氯化物及硫酸盐

目的:建立抑制离子色谱法测定碳酸锂原料药中氯化物及硫酸盐的含量。方法:用Thermo Ion Pac AS11(250 mm×4mm)阴离子交换柱和Ion Pac AG 11(50 mm×4 mm)保护柱,淋洗液为10 mmol·L-1氢氧化钾溶液,由自动淋洗液发生器产生,流速为1.0 ml·min-1,柱温30℃,电导池温度35℃,阴离子抑制器抑制器电流36 m A,进样量10μl。结果:氯离子及硫酸根离子在1.0~20μg·ml-1范围内线性关系良好(r分别为0.995 1,0.997 3),氯离子回收率为106.6%(RSD=2.6%,n=6),硫酸根离子回收率为100.3%(RSD=1.9%,n=6)。结论:该方法准确可靠,可用于碳酸锂原料药中氯化物及硫酸盐的测定。     

反相高效液相色谱法测定吉非替尼原料药含量及有关物质

目的建立吉非替尼原料药含量及有关物质测定的反相高效液相色谱法。方法色谱柱为Sinchroom ODSBP(200 mm×4.6 mm,5μm);以甲醇-水(80:20)为流动相;检测波长为250 nm;流速为1.2 m L·min-1。结果吉非替尼浓度在9.88~148.2μg·m L-1内与峰面积呈良好的线性关系(r=0.999 5,n=6),低、中、高浓度回收率在99.7%~100.4%(RSD<1.5%,n=3)。结论该方法简便快速、准确灵敏、重复性好,能够用于吉非替尼原料药的含量及有关物质的测定。     

HPLC法测定阿普司特原料药的含量

目的建立测定阿普司特原料药含量的方法。方法采用高效液相色谱法。其色谱条件采用Agilent Zorbax SB C18(4.6×250mm,5μm)色谱柱,流动相为甲醇∶20mmol·L-1磷酸二氢铵(p H 3.0)=54∶46(v/v),流速为1.0m L·min-1,检测波长为220nm,进样量为20μL,温度为30℃。结果阿普司特与相邻杂质峰较好分离;其含量测定的线性范围为0.199~0.0199mg·m L-1(r=0.9999);平均回收率为99.88%(n=9),RSD=0.48%(n=6);阿普司特原料药含量测定方法的进样精密度、重复性、稳定性和回收率均符合测定要求。结论本方法操作简便、快捷,结果准确、可靠,可用于阿普司特原料药的质量控制。     

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.

---

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.