HPLC波长切换联合梯度洗脱法同时测定消疲灵颗粒中的7种成分

目的 建立同时测定消疲灵颗粒中7种成分含量的HPLC波长切换联合梯度洗脱方法。方法 采用Venusil MP-C₁₈色谱柱,流动相为乙腈-1%冰醋酸溶液,流速为0.9 mL·min^-1,梯度洗脱,柱温为30 ℃,进样量为10 μL。结果 牡荆素葡萄糖苷、牡荆素鼠李糖苷、牡荆素、金丝桃苷、芒柄花苷、毛蕊异黄酮和芒柄花素检测浓度分别在2.56~51.20 μg·mL^-1,14.87~297.40 μg·mL^-1,2.14~42.80 μg·mL^-1,3.16~63.20 μg·mL^-1,3.80~76.00 μg·mL^-1,2.14~42.80 μg·mL^-1,4.81~ 96.20 μg·mL^-1内与峰面积呈良好的线性关系（r≥0.999 1）,平均回收率97.0%~100.0%,RSD 0.55%~1.67%,精密度和重复性良好,供试品溶液在室温条件下12 h内稳定。结论 该方法操作简便,精密度、稳定性、重复性好,可用于消疲灵颗粒中7种有效成分含量的同时测定。     

HPLC法检测醋酸奥曲肽注射剂中5种抑菌剂

目的：检测醋酸奥曲肽注射剂中是否添加苯酚、苯甲醇、三氯叔丁醇、对羟基苯甲酸甲酯及对羟基苯甲酸丙酯5种抑菌剂。方法：采用C18（L）（4.6 mm×250 mm,5 μm）色谱柱,流动相A为水,流动相B为甲醇,梯度洗脱,流速为1.0 mL·min^-1,柱温30℃,检测波长为220 nm及256 nm。结果：苯酚、苯甲醇、三氯叔丁醇、对羟基苯甲酸甲酯及对羟基苯甲酸丙酯各峰均分离良好;苯酚在1.29~258.60 μg·mL^-1范围内线性关系良好（r=1.000）,平均回收率为100.0%（n=9）;苯甲醇在2.72~544.20 μg·mL^-1范围内线性关系良好（r=0.9997）,平均回收率为100.3%（n=9）;三氯叔丁醇在9.95~1990.00 μg·mL^-1范围内线性关系良好（r=1.000）,平均回收率为100.9%（n=9）;对羟基苯甲酸甲酯在0.27~53.80 μg·mL^-1范围内线性关系良好（r=1.000）,平均回收率为100.5%（n=9）;对羟基苯甲酸丙酯在0.26~52.00 μg·mL^-1范围内线性关系良好（r=1.000）,平均回收率为99.4%（n=9）;91批醋酸奥曲肽注射剂中均未检出5种抑菌剂。结论：该方法准确、灵敏、简便,可用于醋酸奥曲肽注射剂中苯酚、苯甲醇、三氯叔丁醇、对羟基苯甲酸甲酯及对羟基苯甲酸丙酯5种抑菌剂的检查。     

GC-MS测定碳酸司维拉姆中环氧氯丙烷的残留量

目的 建立气相色谱-质谱联用法测定碳酸司维拉姆中环氧氯丙烷残留量的方法,以满足原料药质量标准中的限度要求。方法 采用DB-17MS毛细管柱（30 m×0.25 mm,0.25 μm）;进样口温度为200℃;离子源温度为230℃;MS四极杆温度为150℃;载气为氦气;柱流量为1.0 mL·min^-1;程序升温;分流比为10：1;定量离子m/z 57。结果 在0.087~0.260 μg·mL^-1内环氧氯丙烷浓度与峰面积呈现良好的线性关系,定量限为0.045 μg·mL^-1,检测限为0.017 μg·mL^-1;平均加样回收率为98.4%。结论 该方法简单快速,专属性强,准确度好,灵敏度高,可以满足碳酸司维拉姆原料药标准中的限度要求。     

GC测定白芍总苷原料药中有机溶剂残留

目的 采用GC同时测定白芍总苷原料药中乙醇、乙酸乙酯和正丁醇3种残留溶剂。方法 检测器为氢火焰离子化检测器（FID）,色谱柱为Agilent DB-624石英毛细管柱（30 m×0.53 mm,3.0 μm）,溶剂为N,N-二甲基甲酰胺（DMF）,程序升温。结果 3种残留溶剂均能完全分离,乙醇、乙酸乙酯和正丁醇分别在24.60~491.98 μg·mL^-1（r=0.999 8）,21.01~420.25 μg·mL^-1（r=1.000 0）,23.37~467.48 μg·mL^-1（r=0.999 8）内与峰面积呈良好的线性关系,检测限分别为0.002 37%,0.000 08%和0.000 63%。结论 该方法简单可靠,灵敏度高,可用于白芍总苷原料中的残留溶剂控制。     

UHPLC测定芎菊上清丸中9种成分含量及化学模式分析

目的 建立UHPLC波长切换法同时测定芎菊上清丸中9种成分的含量方法。方法 采用Agilent Ecilipse C₁₈（2.1 mm×100 mm,1.6 μm）色谱柱,流动相：甲醇-0.05%磷酸水溶液,梯度洗脱;流速为0.3 mL·min^-1;检测波长：327,237,320,345,278,254 nm;柱温30℃;进样量2 μL;并采用SPSS 22.0统计软件对含量测定结果进行主成分分析与聚类分析。结果 绿原酸、3,5-二咖啡酰奎宁酸、栀子苷、甘草苷、阿魏酸、盐酸小檗碱、黄芩苷、升麻素苷、5-O-甲基维斯阿米醇苷线性范围分别为4.30~68.80 μg·mL^-1（r=0.999 0）、6.66~106.56 μg·mL^-1（r=0.999 2）、7.67~122.72 μg·mL^-1（r=0.999 4）、4.88~78.08 μg·mL^-1（r=0.999 1）、2.37~37.92 μg·mL^-1（r=0.999 1）、6.50~103.92 μg·mL^-1（r=0.999 2）、8.85~141.60 μg·mL^-1（r=0.999 4）、0.88~14.08 μg·mL^-1（r=0.999 7）、0.74~11.92 μg·mL^-1（r=0.999 3）;平均加样回收率（n=9）均在99.42%~103.10%,RSD均<2.0%。主成分分析与聚类分析均可将不同生产厂家的芎菊上清丸很好地分类,且分类结果一致。结论 所建立的多成分方法快捷、准确、重复性好,可用于芎菊上清丸的质量控制。     

HPLC同时测定消炎利胆片中5种活性成分的含量

目的 建立HPLC同时测定消炎利胆片中5种活性成分（绿原酸、迷迭香酸、穿心莲内酯、芹菜素、脱水穿心莲内酯）的方法。方法 采用phenomonex^®-C₁₈色谱柱（4.6 mm×250 mm,5 μm）,以乙腈（A）-0.4%的磷酸水溶液（B）为流动相进行梯度洗脱,流速为1.0 mL·min^-1,柱温为30℃,检测波长为330 nm（绿原酸、迷迭香酸、芹菜素）和254 nm（穿心莲内酯、脱水穿心莲内酯）。结果 绿原酸、迷迭香酸、穿心莲内酯、芹菜素和脱水穿心莲内酯检测浓度分别在3.042~121.7 μg·mL^-1、2.558~102.3 μg·mL^-1、14.11~564.4 μg·mL^-1、2.835~113.4 μg·mL^-1、23.86~954.3 μg·mL^-1内与峰面积呈良好的线性关系（r ≥ 0.999 6）,平均加样回收率为97.90%~101.75%,RSD为0.89%~1.66%,仪器精密度、重复性、稳定性良好。结论 本试验所建立的方法准确可靠、重复性好,可为消炎利胆片的质量控制提供科学的依据。     

HPLC测定异维A酸有关物质

目的 建立HPLC测定异维A酸有关物质的方法。方法 色谱柱为NUCLEOSIL 100-3 C₁₈（4.6 mm×150 mm,3 μm）,以甲醇-水-冰醋酸（770：225：5）为流动相,流速为1.0 mL·min^-1;柱温为25℃,检测波长为355 nm。结果 异维A酸峰与杂质H、I、维A酸、强制降解杂质峰分离良好;异维A酸、杂质H、I和维A酸的线性范围分别为0.000 545 5~21.82 μg·mL^-1（r=0.999 9）,0.002 856~7.14 μg·mL^-1（r=0.999 0）,0.002 789~6.97 μg·mL^-1（r=0.999 1）、0.017 07~22.76 μg·mL^-1（r=0.999 6）;检测限分别为0.27,0.60,0.65,5.50 ng·mL^-1,定量限分别为0.55,2.85,2.80,17.00 ng·mL^-1;杂质H、I和维A酸的平均回收率分别为101.57%,102.02%,101.03%,RSD分别为0.5%,0.8%,1.5%。结论 建立的HPLC方法准确、专属性强,可用于异维A酸有关物质的测定。     

复方鱼腥草合剂中3个有效成分及防腐剂的含量测定

目的 考察市售复方鱼腥草合剂的质量。方法 收集10批不同厂家生产的复方鱼腥草合剂,应用HPLC测定3个有效成分（绿原酸、连翘酯苷A、黄芩苷）及防腐剂（苯甲酸钠、羟苯乙酯）含量。结果 10批复方鱼腥草合剂中绿原酸的含量为29.74~84.13μg·mL^-1、连翘酯苷A的含量为22.69~113.44 μg·mL^-1、黄芩苷的含量为0.587~1.662 mg·mL^-1;苯甲酸钠和羟苯乙酯含量均符合标准规定。结论 复方鱼腥草合剂质量情况较乐观,但是不同批次内在质量有较大差异,现行标准的质量控制方法较简单,不能有效控制其质量,建议修订完善标准。     

U-SENS™试验方法的建立与探讨

目的 建立符合中国实际情况的U-SENS^™试验方法，并验证新试验方法的可靠性。方法 参考OECD指导原则442E附录II U-SENS^™试验方法，根据其中的QC模板，建立以不同浓度松香酸（20，30，40，50，60，100 μg·mL^-1）为阳性剂的试验系统进行10次试验，应用流式细胞仪技术在人源性淋巴瘤细胞系U937探究最适阳性浓度，并对糖精、对苯二胺、肉桂醇等8个已知其致敏性的化合物进行验证。结果 40，50 μg·mL^-1松香酸能在较小的细胞毒性条件下，表现出稳定的阳性反应，并能对8个已知其致敏性的化合物能进行正确分类。结论 以松香酸为阳性剂建立U-SENS™试验系统可行，可选用终浓度40 μg·mL^-1或50 μg·mL^-1作为阳性对照浓度，确保该试验系统能对受试物的皮肤致敏性进行准确分类。     

HPLC同时测定通脉颗粒中丹参素、原儿茶醛、丹酚酸B、阿魏酸和葛根素的含量

目的 建立通脉颗粒中丹参素、原儿茶醛、丹酚酸B、阿魏酸和葛根素的HPLC测定方法。方法 采用Welch Ultimate XD-C₁₈色谱柱（4.6 mm×250 mm,5 μm）,以乙腈-0.1%三氟乙酸为流动相,梯度洗脱,双波长检测（282,305 nm）,柱温35℃,流速1.0 mL·min^-1。结果 丹参素、丹酚酸B、原儿茶醛、葛根素和阿魏酸的线性范围分别为3.117~62.33 μg·mL^-1（r=0.998 7）,4.044~80.88 μg·mL^-1（r=0.9985）,1.280~25.60 μg·mL^-1（r=0.997 9）,7.964~159.3 μg·mL^-1（r=0.992 8）,1.980~39.60 μg·mL^-1（r=0.999 1）;平均回收率分别为101.6%（RSD=1.62%）,99.7%（RSD=1.76%）,97.4%（RSD=1.19%）,99.9%（RSD=1.52%）,102.2%（RSD=1.56%）。结论 该方法操作简便、快速,结果准确,可用于通脉颗粒的质量控制。     

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.     

Nachweis einiger Heilmittel in der Kniegelenksynovialflüssigkeit

Zusammenfassung Mittels Gaschromatographie und Dünschichtchromatographie wiesen die Autoren 11 Substanzen nach, welche durch Injektion oder nach Verabreichung per os in die Kniegelenksynovialflüssigkeit eindrangen. In ihrer Aufstellung konnten sie eine direkte Beziehung zwischen Struktur sowie chemischphysikalischen Eigenschaften der Substanz und ihrer Fähigkeit, aus dem Blut in die Kniegelenksynovialflüssigkeit einzudringen, nicht nachweisen, außer der Tatsache, daß Substanzen mit starker Affinität zu Eiweißstoffen erst in höheren Dosen nachweisbar waren.     

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.     

Biochemical and molecular characterisation of cubozoan protein toxins

Class Cubozoa includes several species of box jellyfish that are harmful to humans. The venoms of box jellyfish are stored and discharged by nematocysts and contain a variety of bioactive proteins that are cytolytic, cytotoxic, inflammatory or lethal. Although cubozoan venoms generally share similar biological activities, the diverse range and severity of effects caused by different species indicate that their venoms vary in protein composition, activity and potency. To date, few individual venom proteins have been thoroughly characterised, however, accumulating evidence suggests that cubozoan jellyfish produce at least one group of homologous bioactive proteins that are labile, basic, haemolytic and similar in molecular mass (42-46 kDa). The novel box jellyfish toxins are also potentially lethal and the cause of cutaneous pain, inflammation and necrosis, similar to that observed in envenomed humans. Secondary structure analysis and remote protein homology predictions suggest that the box jellyfish toxins may act as α-pore-forming toxins. However, more research is required to elucidate their structures and investigate their mechanism(s) of action. The biological, biochemical and molecular characteristics of cubozoan venoms and their bioactive protein components are reviewed, with particular focus on cubozoan cytolysins and the newly emerging family of box jellyfish toxins.     

Dose tolerability of chronically inhaled voriconazole solution in rodents

Invasive pulmonary aspergillosis (IPA) is a fungal disease of the lung associated with high mortality rates in immunosuppressed patients despite treatment. Targeted drug delivery of aqueous voriconazole solutions has been shown in previous studies to produce high tissue and plasma drug concentrations as well as improved survival in a murine model of IPA. In the present study, rats were exposed to 20 min nebulizations of normal saline (control group) or aerosolized aqueous solutions of voriconazole at 15.625 mg (low dose group) or 31.25 mg (high dose group). Peak voriconazole concentrations in rat lung tissue and plasma after 3 days of twice daily dosing in the high dose group were 0.85 ± 0.63 μg/g wet lung weight and 0.58 ± 0.30 μg/mL, with low dose group lung and plasma concentrations of 0.38 ± 0.01 μg/g wet lung weight and 0.09 ± 0.06 μg/mL, respectively. Trough plasma concentrations were low but demonstrated some drug accumulation over 21 days of inhaled voriconazole administered twice daily. Following multiple inhaled doses, statistically significant but clinically irrelevant abnormalities in laboratory values were observed. Histopathology also revealed an increase in the number of alveolar macrophages but without inflammation or ulceration of the airway, interstitial changes, or edema. Inhaled voriconazole was well tolerated in a rat model of drug inhalation.