环孢素原料药中残留溶剂检测方法的研究

目的 检查环孢素原料药中的有机溶剂残留量.方法 采用气相色谱法,色谱柱为弹性石英毛细管柱SE - 54(聚甲基苯基乙烯基硅氧烷为固定液,30 m×0.53 mm×2.5 μm),进样口温度200℃;氢火焰离子化检测器(FID)温度:250℃;柱温:程序升温,初始温度55℃,维持1 min,以10℃/min的速率升温至1...     

顶空气相色谱法测定盐酸左布比卡因中残留溶剂

目的:建立盐酸左布比卡因原料药中有机溶剂残留量的测定方法.方法:采用内标法项空进样毛细管气相色谱法,测定盐酸左布比卡因原料中有机溶剂残留量.色谱柱为DB - 624毛细管柱(30m×0.53mm,3.0μm),载气为氮气,FID检测器;程序升温,在60℃下保留5min,然后以20℃/min的速率升温至200℃,保持10min;进样口温度220℃,检测器温度240℃,分流比为1∶1.结果:质量浓度在范围内与峰面积线性关系良好,r为0.999 98,平均回收率为103.2％,精密度的RSD为0033％,最低栓出限为0.14μg/mL.结论:该方法可用于盐酸左布比卡因中有机溶剂残留量的测定.     

GC法测定法罗培南钠有机溶剂残留量

目的:建立法罗培南钠原料药中有机溶剂残留量测定方法。方法:采用气相色谱法测定,色谱柱为HP-5弹性石英毛细管柱(30 m×0.53 mm,1.5 μm,以5％苯基-95％甲基聚硅氧烷为固定液),进样口温度:200℃,氢火焰离子化检测器(FID),检测器温度:250℃;柱温:程序升温,初始温度35℃,保持5 min,以每分钟10℃的升温速率升温至120℃,保持2 min,再以每分钟35℃的升温速率升温至250 ℃,保持5 min,载气:氮气,流速:2 mL/min,分流比:1:1,尾吹流速:30mL/min,以N-甲基吡咯烷酮为溶剂。结果:待测物均能得到很好的分离,峰面积与浓度呈良好的线性关系,精密度良好。结论:该法可用于法罗培南钠原料药中有机溶剂残留量的检测。     

(+)2-氨基丁醇合成工艺中残留溶剂的研究

目的:建立GC法测定(+)2-氨基丁醇中有机溶剂的残留量.方法:色谱柱为J&W DB-SELECT 624UI,以起始温度40℃程序升温8min,8℃/min的速率升温至120℃,维持7min;进样口温度为200℃,检测器温度为250℃;载气为氮气,流速2mL/min;分流比为40:1;进样量为1μL.结果:甲醇线性范...     

顶空气相色谱法测定氯法拉滨中有机溶剂残留量

目的建立顶空气相色谱法测定氯法拉滨中有机溶剂残留量。方法采用Agilent DB-624弹性石英毛细管柱(30 m×0.53 mm,3.0μm),火焰离子化检测器(FID),载气为氮气;进样口温度170℃;检测器温度:300℃;分流比:30∶1;柱压力12 kPa;柱温:程序升温,初始温度40℃,维持1 min,以15℃/min的速率升温至250℃,维持1 min。顶空进样,平衡温度为80℃,平衡时间30 min。以N,N-二甲基乙酰胺为溶剂,外标法测定。结果被测物均能得到很好的分离,峰面积与浓度呈良好的线性关系,精密度良好。结论该法简便、准确、灵敏度高,可用于氯法拉滨有机溶剂残留量检测。     

顶空毛细管气相色谱法测定阿托伐他汀钙原料药中残留溶剂

目的:建立阿托伐他汀钙原料药中甲醇、丙酮、叔丁醇、正丁醇4种有机溶剂残留量的测定方法。方法:采用顶空毛细管气相色谱法, DB-624石英毛细管柱,检测器为氢火焰离子化检测器,载气为氦气,流速为5.0mL/min,柱温采用程序升温（初始温度40℃,维持3mim,15℃/min 的速率升温至150℃,维持2min,再以30℃/min 的速率降至40℃,维持8分钟）,进样口温度为180℃,检测器温度为260℃,顶空温度为100℃,平衡时间为30 min,分流比为2:1,定量环温度为100℃,传输管温度为110℃,进样体积为2mL。结果:4种有机溶剂在该色谱条件下均能有效分离,峰面积与浓度呈现良好线性关系,精密度、回收率良好。结论:该方法准确、可靠,专属性强,灵敏度高,可用于阿托伐他汀钙原料药中残留溶剂的含量测定。     

毛细管气相色谱法测定氟马西尼中有机溶剂残留量

目的建立测定氟马西尼原料药中乙醇、叔丁醇、二氯甲烷、N,N-二甲基甲酰胺(DMF)和二甲亚砜(DMSO)残留量的毛细管气相色谱法。方法采用直接进样法,以甲醇为溶剂。色谱柱为HP-5柱(0.53 mm×30 m,5.0μm);载气为氮气;分流进样,分流比为8∶1;进样口温度为250℃;检测器为氢火焰离子检测器(FID),温度为280℃;采用程序升温:柱温起始为45℃,保持5 min,然后以20℃.min-1的升温速率升温至200℃。结果五种有机溶剂在6~128μg.mL-1浓度范围内线性关系良好,平均回收率在98%~104%之间。结论本法能快速准确地对氟马西尼中5种有机残留溶剂进行检测,满足了对氟马西尼生产工艺中的溶剂残留的的控制要求。     

气相色谱法测定阿立哌唑原料药中4种有机溶剂残留量

目的 建立阿立哌唑原料药中残留有机溶剂乙醇、乙腈、二氯甲烷、N,N-二甲基甲酰胺的气相色谱测定方法 .方法 采用AC-1毛细管色谱柱(30m×0.53mm×1.0μm);氮气为载气;初始柱温为40℃,保持3min后以40℃/min的速率升至160℃,保持2min;氢火焰离子化检测器温度为200℃;进样口温度为160℃;进样量为1μL.结果 阿立哌唑原料药中的4种有机溶剂完全分离,在所考察的浓度范围内均具有良好的线性关系,加样回收率在98.1%~99.0%范围内.3批阿立哌唑样品中均未检出4种有机溶剂.结论 该方法 准确、灵敏度高,适用于阿立哌唑原料药中有机溶剂残留量的测定.     

气相色谱法测定盐酸阿比多尔中6种残留溶剂

目的:建立气相色谱法(GC)测定盐酸阿比多尔中的丙酮、甲醇、乙醇、异丙醇、二氯甲烷和三氯甲烷6种有机溶剂残留量。方法:采用Thermo WAX气相色谱柱(30 m×0.25 mm,0.25μm);FID检测器;进样口温度为220℃,检测器温度为240℃;载气为氮气,载气流速为2 mL·min^-1;采用程序升温法:起始温度为40℃,保持10 min,以40℃·min^-1的速率升温至200℃,保持5 min。结果:6种残留溶剂在各自浓度范围内线性关系良好(r>0.999);平均回收率为95.91%~102.29%,RSD为1.90%~3.67%。结论:本法操作简单、准确度高、重现性好,可用于盐酸阿比多尔原料药中6种有机溶剂残留量的测定。     

顶空毛细管气相色谱法测定奥曲肽中有机溶剂残留量

目的建立气相色谱法测定奥曲肽中有机溶剂二氯甲烷、吡啶、N,N-二甲基甲酰胺残留量的方法。方法采用顶空毛细管气相色谱法,应用DB-624大口径毛细管柱(30 m×0.53 mm×3μm);氢火焰离子化检测器,以水为溶剂,初始柱温为60°C维持3 min,以10℃/min的速率升温至160℃,维持3 min,进样口温度:140℃;检测器温度:250℃;以高纯氮气为载气,流速3.0 ml/min;分流比为5∶1,实现各组分的基线分离。结果此法具有良好的线性,r在0.999 5~1之间,RSD小于5%(n=5)。结论经方法学验证,该方法灵敏度、准确度均达到有机溶剂残留量的检测要求,可用于原料药奥曲肽中残留溶剂的检测。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

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.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

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.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.