固相萃取-气相色谱-质谱联用法测定白术中8种有机氯农药的残留量

目的：建立固相萃取-气相色谱-质谱联用法同时测定白术中8种有机氯农药残留量。方法：样品以丙酮超声提取,采用氨基固相萃取柱进行净化,气相色谱-质谱联用技术进行测定。结果：8种有机氯农药在10~1 000μg/L范围内呈良好的线性关系,8种农药的检测限在0.3~2.0μg/kg之间,定量限在1.0~6.0μg/kg之间,3个水平添加回收率在82.07%~105.13%之间,相对标准偏差（RSD）〈6%（n=9）。结论：本方法灵敏度高,重现性好,可用于白术中8种有机氯农药残留量的检测。     

UHPLC-MS/MS测定大鼠尿液中环磷酰胺及其代谢产物浓度

目的 基于超高效液相色谱-串联质谱法（UHPLC-MS/MS）,建立测定给予高剂量环磷酰胺（cyclophosphamide,CTX）后大鼠尿液中CTX及其代谢产物脱氯乙基环磷酰胺（dechloroethylcyclophosphamide,DCCTX）、4-酮基环磷酰胺（4-Ketocyclophosphamide ,4-KetoCTX）、羧基磷酰胺（Carboxyphosphamide ,CEPM）浓度的方法。方法 大鼠尿液样品经10%甲醇水溶液直接稀释,离心后取上清液,采用UHPLC-MS/MS法进行检测分析。色谱柱：Agilent poroshell SB-C18 (2.1 mm × 75 mm,2.7 μm);流动相：甲醇-10 mmol?L-1乙酸铵水溶液,进行梯度洗脱,流速0.25 mL?min-1,柱温25 °C。采用电喷雾离子源,以多重反应监测模式进行正离子检测。用于定量检测分析的离子对分别为：CTX：m/z 261.10→140.10;DCCTX：m/z 199.20→78.00;4-KetoCTX：m/z 275.10→142.00;CEPM：m/z 293.10→221.10;替硝唑（tinidazole,TNZ）：m/z 248.10→121.10。结果 CTX及其代谢产物尿中浓度在40~2000 ng?mL-1范围内线性关系良好（CTX、DCCTX、4-KetoCTX、CEPM的r2分别为：0.9915,0.9910,0.9956,0.9918）,最低定量限均为40 ng?mL-1;日内、日间RSD分别为0.67%~12.76%、1.30%~11.92%;由内标归一化的基质因子计算RSD,结果在0.52%~7.60%之间;该方法的提取回收率为74.00%~102.70% （n=6）,方法回收率为85.89%-110.69% （n=5）;测定成分和内标的稳定性均良好。结论 该方法快捷、准确可靠、重复性好,适用于大鼠高剂量CTX给药后CTX及其代谢产物尿药浓度的测定及排泄研究。     

反相高效液相色谱法测定当归补血口服液中阿魏酸的含量

目的建立反相高效液相色谱法（RP-HPLC）测定当归补血口服液中阿魏酸的含量。方法固定相 ：Shim Pack vp ODS（150 mm×4.6 mm），流动相：0.2%甲醇乙腈∶0.1%磷酸0.1%三乙胺水溶液（20∶80），流速1.00 mL·min^-1，柱温：室温，检测波长324 nm。 结果阿魏酸在0.80～20.00 mg·L^-1范围内线性关系良好。平均加样回收率为98.42%，RSD为1.62%。结论该方法简便，快速、灵敏、重复性好，可作为该制剂的质量控制指标。     

HPLC法测定艾拉戈克钠原料药中手性异构体的研究

目的：建立测定艾拉戈克钠原料药中艾拉戈克钠手性异构体的HPLC方法。方法：采用CHIRALPAK ZWIX（-）色谱柱，以甲醇-乙腈-水-甲酸-二乙胺（170∶810∶20∶0.38∶0.52）为流动相，检测波长为270 nm，流速0.5 mL·min-1，进样量10 μL，柱温25℃，运行时间20 min。结果：艾拉戈克钠手性异构体与艾拉戈克钠之间分离度良好，质量浓度在 0.25 ~ 10 μg·mL-1范围内峰面积线性关系良好（r > 0.999）；定量限约为0.25 μg·mL-1，检测限约为0.1 μg·mL-1；回收率在94.33% ~ 109.1%之间（RSD 4.0%），3批次样品中均未检出艾拉戈克钠异构体。结论：建立的艾拉戈克钠手性异构体高效液相检查法专属性强、灵敏度适宜、重复性良好，可适用于艾拉戈克钠其手性异构体的质量控制。     

UHPLC-MS/MS法测定依那普利氢氯噻嗪复方制剂中潜在基因毒性杂质

目的 通过合成基因毒性杂质N-亚硝基氢氯噻嗪（NO-HZCT），建立超高效液相色谱-串联质谱法（UHPLC-MS/MS）测定依那普利氢氯噻嗪制剂中N-亚硝基氢氯噻嗪。方法 参考文献方法合成NO-HZCT，采用高分辨质谱对其相对分子量和结构进行确定；采用Agilent EclipsePlus C₁₈ RRHD（3.0 mm×150 mm，1.8 μm）色谱柱，以10 mmol•L^-1甲酸铵-0.1%甲酸的水溶液作为流动相A，以0.1%甲酸的乙腈溶液作为流动相B，梯度洗脱，体积流量0.6 mL•min^-1；采用ESI离子源正离子扫描，多反应监测（MRM）模式下，对NO-HZCT进行定量检测。结果 NO-HZCT质量浓度在0.51~50.67 ng·mL^-1范围内具有良好的线性关系，相关系数（r）为0.999 7；低、中、高3个浓度的加样回收率（n=3）分别为93.10%（RSD 3.7%）、104.30%（RSD 1.0%）和106.48%（RSD 1.8%）；检测限和定量限分别为0.08 ng•mL^-1和0.27 ng•mL^-1，3批样品中均检测出NO-HZCT。结论 该方法灵敏度高、专属性强，可准确地对依那普利氢氯噻嗪制剂中遗传毒性杂质NO-HZCT进行定量检测，可为依那普利氢氯噻嗪制剂的质量控制提供参考，保障药品质量安全。     

基于液-质联用法研究10-羟喜树碱在大鼠体内的药动学行为

目的：建立测定大鼠血浆中10-羟喜树碱浓度的液相色谱-串联质谱（LC/MS-MS）分析方法，并用于10-羟喜树碱注射液经时血药浓度的验证评价。方法：血浆样品经乙酸乙酯（含0.2%冰醋酸）提取处理，以0.1%甲酸-乙腈与0.1%甲酸-水溶液为流动相，梯度洗脱。采用电喷雾离子源（ESI）在正离子条件下，通过多反应监测模式（MRM）进行检测。结果：10-羟喜树碱的血浆浓度在7.812 5~1 000 ng·mL^-1范围内线性关系良好，日内与日间精密度的RSD均小于5%，提取回收率为91.73%~106.22%。结论：该方法快速且操作简单，适用于10-羟喜树碱及其一些制剂给药后的基础和临床药动学分析评价。     

HPLC法测定盐酸伊立替康注射液的含量和有关物质

目的：建立盐酸伊立替康注射液含量及有关物质测定的方法。方法：采用高效液相色谱法,色谱柱为Hypersile Luna（2）C18,流动相为水溶液（含0.02mol/L磷酸二氢钠和0.008mol/L辛烷磺酸钠）-乙腈-甲醇（59∶17∶24,V/V/V）,流速为1.5ml/min,检测波长为255nm,柱温为40℃。结果：盐酸伊立替康检测质量浓度线性范围为98.5～985.0μg/m（lr=0.99997）,检测限为1.2ng;高、中、低3种浓度水平的平均回收率分别为99.4%、99.8%、99.6%（n=3）,RSD分别为0.12%、0.10%、0.15%（n=3）。结论：建立的方法准确,适用于盐酸伊立替康制剂的质量控制。     

反相高效液相色谱法测定茵陈药材及其制剂中绿原酸含量

目的 建立测定茵陈药材及其制剂中绿原酸含量的高效液相色谱法。方法固定相：Kromasil C18 色谱柱(4.6 mm×250 mm,5 μm)；流动相：乙腈 0.1%磷酸（9：91）；检测波长：327 nm；流速：0.9 mL·min－1；柱温：40 ℃；进样量：10 μL。结果绿原酸在4.9～78.4 μg·mL－1浓度范围内线性关系良好（r＝0.999 7）；绿原酸平均回收率（n=3）分别为98.5%(RSD=1.32%)，99.0%(RSD=0.81%)，98.4%（RSD=0.52%）。结论 该方法灵敏快速、准确可靠，可作为茵陈药材及其制剂中绿原酸的质量控制方法。     

RP-HPLC法测定香苏正胃丸中厚朴酚及和厚朴酚的含量

目的：建立测定香苏正胃丸中厚朴及和厚朴酚含量的RP-HPLC方法。方法：采用高效液相色谱法测定处方中厚朴酚及和厚朴酚的含量,色谱条件以十八烷基硅烷键合硅胶为填充剂;以甲醇-乙腈-水（5∶2∶5）为流动相;检测波长为294 nm,柱温40℃;流速1 ml/min。结果：HPLC方法学考查结果表明和厚朴酚在0.081 8~0.818μg（r=0.999 9）、厚朴酚在0.065 9~0.659μg（r=0.999 9）范围内线性良好;平均加样回收率和厚朴酚、厚朴酚分别为100.13%（RSD 1.7%）、96.75%（RSD 1.6%）。结论：该方法快捷、准确,可有效地控制制剂质量。     

25种常用中药饮片常见真菌毒素污染分布比较研究

目的 建立中药饮片10种真菌毒素的超高效液相色谱三重四极杆质谱联用方法,并对市售25批中药饮片的真菌毒素污染分布比较研究。方法 样品经70%甲醇超声处理,HLB固相萃取柱净化,Waters ACQUITY UPLC^®BEH C₁₈(2.1 mm×100 mm,1.7 μm)分离,流动相为乙腈-甲醇(1:1)和0.01%甲酸水溶液梯度洗脱,ESI离子源正离子扫描,通过多反应检测模式测定,外标法定量。结果 10种真菌毒素在0.31~250 ng·mL^-1内线性关系良好,相关系数均>0.991,平均加样回收率为83.60%~131.80%,RSD为2.35%~7.85%,10种真菌毒素的检出限为0.14~16.30 ng·kg^-1。25批中药材中,伏马毒素B2检出率最高(28%),其次为呕吐毒素(20%);黄曲霉素B2等4种真菌毒素未检出;果实种子类真菌毒素污染最严重(66.7%),动物类药材真菌毒素污染率最低(20%)。结论 本方法可用于中药饮片中10种真菌毒素的检测;除了黄曲霉毒素外,对于中药饮片中其他真菌毒素应加强监测,其中尤其应注意果实种子类中药的真菌毒素监测。     

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.

     

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.     

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.     

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.