RP-HPLC法测定葡醛酸钠注射液的含量

目的建立测定葡醛酸钠注射液含量的反相高效液相色谱法。方法色谱柱:Agilent Zorbax Sb-C18(150mm×4.6mm,5μm);流动相:磷酸盐缓冲液(6mmol.L-1NaH2PO4+4mmol.L-1Na2HPO4)-甲醇(98∶2,磷酸调pH至6.0±0.05);流速:0.6mL·min-1;检测波长:225nm。结果葡醛酸钠在0.1~2mg.mL-1范围内线性关系良好,r=0.9999,平均回收率为100.2%(n=9)。结论该方法简便,结果准确可靠,可作为葡醛酸钠注射液的质量控制方法。     

反相高效液相色谱法测定注射用哌拉西林钠/舒巴坦钠的含量

目的 :建立注射用哌拉西林钠 /舒巴坦钠的含量及有关物质测定方法。方法 :采用C18柱 ,流动相为 :甲醇 0 .2moL·L-1磷酸二氢钾溶液 10 %四丁基氢氧化铵溶液 水 (5 10∶5 0∶8∶432 ) ,pH4.1,检测波长为 2 30nm ,流速 0 .8mL·min-1。结果 :线性范围为舒巴坦 5 .1～ 6 0 6 .3mg·L-1,哌拉西林 13 .2～ 15 83.1mg·L-1,回收率哌拉西林为 (99.6± 0 .5 ) % ,舒巴坦 (10 0 .2±0 .8) % ,最低检测限为 2 .2 2ng和 0 .94ng。结论 :本法简便、专属、重现性好 ,可同时测定哌拉西林和舒巴坦含量 ,亦可用于有关物质检查。     

HPLC法测定注射用阿洛西林钠舒巴坦钠中的有关物质

目的利用HPLC法测定注射用阿洛西林钠舒巴坦钠中的有关物质。方法采用Hypersil C18(250 mm×4.6 mm,5μm)为色谱柱,以水-乙腈-磷酸盐缓冲液(pH值5.8)(体积比30∶30∶100)为流动相,流速为1.0 mL·min-1,检测波长为210 nm。结果在该色谱条件下,阿洛西林与舒巴坦分离良好,阿洛西林钠有关物质测定中阿洛西林钠的质量浓度在0.408²0.4 mg·L-1内线性关系良好,r=0.999 0,舒巴坦钠有关物质测定中舒巴坦钠的质量浓度在1.13220.4 mg·L-1内线性关系良好,r=0.999 0,舒巴坦钠有关物质测定中舒巴坦钠的质量浓度在1.132²2.64 mg·L-1内线性关系良好,r=0.999 9;阿洛西林钠最低检出限为81.2μg·L-1,舒巴坦钠最低检出限为0.566 mg·L-1;阿洛西林钠最低定量限为0.406 mg·L-1,舒巴坦钠最低定量限为1.132 mg·L-1。结论该方法简便、灵敏、准确可靠,可有效测定注射用阿洛西林钠舒巴坦钠中的有关物质。     

HPLC法测定注射用脱氧核苷酸钠的含量

目的建立高效液相色谱法测定注射用脱氧核苷酸钠的含量。方法采用Whatman TMPartisil-10 SAX(250mm×4.6mm,10μm)色谱柱,流动相为50mmol·L-1磷酸二氢钾溶液(取磷酸二氢钾6.80 g,加水800mL,用磷酸调节pH至3.3,加水稀释至1 000mL),柱温为30℃,检测波长为258 nm,流速为1.0mL·min-1。结果注射用脱氧核苷酸钠中脱氧核糖胞嘧啶核苷酸钠(d CMPNa)、脱氧核糖腺嘌呤核苷酸钠(d AMP-Na)、脱氧核糖胸腺嘧啶核苷酸钠(d TMP-Na)和脱氧核糖鸟嘌呤核苷酸钠(d GMP-Na)的质量浓度分别在0.900 0~90.30mg·L-1、0.940 0~94.70mg·L-1、0.880 0~87.60mg·L-1和0.740 0~74.00mg·L-1内与峰面积呈良好的线性关系,且r均大于0.999 5。4种脱氧核糖核苷酸钠的平均加样回收率分别为99.3%(RSD=1.2%)、99.1%(RSD=0.8%)、98.2%(RSD=1.1%)和100.1%(RSD=1.5%)(n=9)。结论该方法简便、专属,分离效果好,灵敏度高,可用于测定注射用脱氧核苷酸钠中4种脱氧核糖核苷酸钠的含量。     

注射用头孢西丁钠他唑巴坦钠的有关物质及稳定性研究

目的建立反相高效液相色谱方法测定注射用头孢西丁钠他唑巴坦钠(质量比4∶1)中的有关物质,并对其稳定性进行研究。方法采用Diamonsil C18色谱柱(250 mm×4.6 mm,5μm),以30 mmol·L-1磷酸二氢钾溶液-体积分数10%四丁基氢氧化铵(体积比98∶2)、用体积分数85%磷酸调节pH值4为流动相A,以乙腈为流动相B,梯度洗脱。流速1.0 mL·min-1,进样量10μL,柱温30℃,在波长230 nm下测定注射用头孢西丁钠他唑巴坦钠(质量比4∶1)中的有关物质。结果头孢西丁钠和他唑巴坦钠分别与其相邻杂质峰能完全分离。在光照、加速、长期试验条件下,有关物质略有增加,在其他影响因素条件下,有关物质无明显变化,在贮存过程中头孢西丁钠和他唑巴坦钠的含量都有降低,有关物质和含量的变化在建立的标准范围内。结论该方法简便、准确、专属性好,适用于该产品的质量分析。注射用头孢西丁钠他唑巴坦钠(质量比4∶1)在贮藏过程中基本稳定。     

HPLC测定注射用呋布西林钠的含量及有关物质

目的 建立注射用呋布西林钠的含量及有关物质的HPLC测定方法.方法 采用C18柱;以磷酸盐缓冲液(0.1 mol·L-1磷酸二氢钾溶液,用磷酸调pH 3.5)∶乙腈(80∶20)为流动相A;以磷酸盐缓冲液(0.1 mol·L-1磷酸二氢钾溶液,用磷酸调pH 3.5)∶乙腈(75∶25)为流动相B,含量测定以流动相B等度洗脱,有关物质采用线性梯度洗脱;流速1.0 mL·min-1;检测波长为225 nm.结果 呋布西林钠的线性范围为0.022 56～0.902 4 mg·mL-1,r为0.999 9,平均加样回收率为100.1%,RSD为0.65%(n=9).结论 方法简便、准确、灵敏度高,可同时用于产品的产量控制及有关物质检查.     

脱氧核苷酸钠制剂的有关物质研究

目的建立HPLC法测定注射用脱氧核苷酸钠和脱氧核苷酸钠注射剂中的有关物质,并应用LC-MS/MS法推测有关物质结构。方法采用HPLC法测定2种脱氧核苷酸钠制剂中的有关物质。色谱柱为Agilent Zorbax SAX柱(250 mm×4.6 mm,5μm),流动相为浓度50 mmol·L-1的磷酸二氢钾溶液(取6.80 g磷酸二氢钾,加水800 m L,用磷酸调p H值至3.3,再加水稀释至1 000 m L),流速为0.6 m L·min-1,柱温为30℃,进样量为20μL,检测波长为258 nm。结果 2种脱氧核苷酸钠制剂中脱氧核糖胞嘧啶核苷酸钠(d CMP-Na)、脱氧核糖腺嘌呤核苷酸钠(d AMP-Na)、脱氧核糖胸腺嘧啶核苷酸钠(d TMP-Na)和脱氧核糖鸟嘌呤核苷酸钠(d GMP-Na)分别与其相邻色谱峰完全分离,测得的注射用脱氧核苷酸钠中最大单个有关物质百分含量均不大于2.0%,有关物质总量均不大于4.0%。脱氧核苷酸钠注射剂中最大单个有关物质百分含量平均大于30%,而有关物质总量更是达到79%以上。经质谱分析,推测注射用脱氧核苷酸钠有关物质为5-甲基胞嘧啶脱氧核糖核苷酸,脱氧核苷酸钠注射剂有关物质为胞嘧啶核糖核苷酸、尿嘧啶核糖核苷酸和鸟嘌呤核糖核苷酸。结论该方法简便,准确,专属性较好,适用于脱氧核苷酸钠制剂的质量分析,为脱氧核苷酸钠制剂临床用药的安全性改善提供参考。     

HPLC法测定注射用单磷酸阿糖腺苷中的有关物质

目的:建立测定注射用单磷酸阿糖腺苷中有关物质的高效液相色谱法。方法:采用Kromasil 100-5 C18(250 mm×4.6 mm,5μm)色谱柱,以水(含10 mmol·L-1四丁基氢氧化铵与10 mmol·L-1磷酸二氢钾)-甲醇(80∶20)为流动相;流速为1.0 ml·min-1,检测波长:258 nm,柱温:30℃;进样量:20μl;应用外标法对注射用单磷酸阿糖腺苷中已知杂质阿糖腺苷和腺嘌呤进行检查,其他未知杂质用主成分自身对照法进行检查。结果:阿糖腺苷和腺嘌呤分别在0.0765~1.530 7μg·ml-1(r=0.999 9),0.078 0~1.560 0μg·ml-1(r=0.999 9)范围内线性关系良好,平均回收率分别为99.8%(RSD=0.2%,n=9)、97.0%(RSD=1.2%,n=9)。结论:该方法可用于注射用单磷酸阿糖腺苷有关物质的测定。     

血浆钠对利尿剂作用的影响

目的 :对血浆钠 <130mmol·L-1,利尿剂作用减弱 ,腹水消失时间延长的 5 6例肝硬化腹水病人 ,静脉补充 3%氯化钠(NaCl) ,观察利尿剂作用的效果。方法 :根据血浆钠检测结果及尿量变化 ,日补充 3%NaCl 30 0ml,连续使用 1～ 7d ,平均每人输注 45 5 .8ml。结果 :输注 3%NaCl后 6h尿量开始增加 ,2 4h增加 5 0 0～ 15 0 0ml,利尿剂作用明显增强 ,腹水消失时间缩短 ,与对照组相比差异具有显著性 (P <0 .0 1)。结论 :血浆钠 <130mmol·L-1时利尿剂作用明显减弱 ,血浆钠越低 ,利尿剂作用越弱。应用利尿剂时应注意NaCl的补充     

更昔洛韦葡萄糖注射液中有关物质的检查

目的　建立更昔洛韦葡萄糖注射液中有关物质的检查方法。方法　采用HPLC法,确定了有关物质检查的最佳条件。用HypersilC18色谱柱(2 5 0mm×4 . 6mm ,10 μm) ,甲醇- 0 0 2mol·L-1KH2 PO3 (6∶94 )为流动相,流速1 0ml·min-1,在2 5 2nm处,采用杂质峰面积对照法对鸟嘌呤进行检查,采用不加校正因子的主成分自身对照法对其他有关物质进行检查。结果　鸟嘌呤及其他有关物质的最低检测限均为0 . 4ng(S/N =3) ,方法重复性的RSD分别为1 .30 %和1 .38% (n =6 )。结论　方法专属性强,灵敏度高,精密度好,可用于质量控制。     

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.

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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.     

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.