HPLC测定甘氨双唑钠中的有关物质

目的 建立高效液相色谱法测定甘氨双唑钠中的有关物质。方法 采用资生堂 CAPCELL C₁₈色谱柱(250 mm×4.6 mm,5 μm)色谱柱,以0.05 mol·L^-1醋酸铵溶液(用氢氧化钠试液调pH值至7.1)-乙腈(80∶20)为流动相,流速：1.0 mL·min^-1, 检测波长：316 nm,柱温：35 ℃,进样量：20 μL。结果 甘氨双唑钠及其相关杂质均能较好分离。甘氨双唑钠在0.46~18.42 μg·mL^-1内线性关系良好(r=0.999 9),甲硝唑在0.04~20.12 μg·mL^-1内线性关系良好(r=1.000 0),平均回收率为98.81%(RSD=0.90%)。结论 本方法灵敏,准确,专属性强,可用于甘氨双唑钠中有关物质的测定。     

头孢克洛分散片中聚合物测定

目的 建立2种头孢克洛聚合物有效的测定方法并对结果进行比较。方法 方法1：采用TSKgel G2000SWxl色谱柱（7.8 mm×300 mm,5 μm）,流动相为0.01 mol·L^-1磷酸盐缓冲液[0.01 mol·L^-1 NaH₂PO₄溶液-0.01 mol·L^-1 Na₂HPO₄溶液（50︰50）,调节pH值为7.0]-乙腈（95︰5）,流速为0.5 mL·min^-1柱温35℃,检测波长为254 nm,进样量20 μL;方法2：采用Sephadex G-10色谱柱（10 mm×300 mm,40~120 μm）,以0.05 mol·L^-1磷酸盐缓冲液[取0.05 mol·L^-1 Na₂HPO₄溶液-0.05 mol·L^-1 NaH₂PO₄溶液（50︰50）,调节pH至7.0]为流动相A,水为流动相B,流速为1 mL·min^-1,柱温35℃,检测波长为254 nm,进样量100 μL。结果 方法1：头孢克洛主峰与聚合物峰分离度>1.5,头孢克洛质量浓度在0.25~20 μg·mL^-1内线性关系良好（r=0.999 9）;定量限0.21 μg,检测限0.07 μg。重复性较好（RSD为1.8%,n=6）;在拟定的色谱条件下,通过考察破坏坏性实验（高温、强酸、强碱、氧化、光照）能够满足分离度要求,辅料无干扰;方法2：质量浓度在2.5~20 μg·mL^-1线性关系良好（r=0.999 7）;检测限0.13 μg,定量限0.40 μg。重复性良好（RSD为1.8%,n=6）。结论 新建立的2种方法对于头孢克洛分散片聚合物的分离度好,分离效率高,重复性好,均可以作为头孢克洛分散片的质量控制的依据。     

HPLC同时测定黄石感冒片中阿魏酸、芦丁、大黄酸、大黄素和大黄酚的含量

目的 建立HPLC同时测定黄石感冒片中阿魏酸、芦丁、大黄酸、大黄素和大黄酚的含量。方法 采用HPLC,色谱柱为Welch Topsil-C₁₈柱(4.6 mm×250 mm,4 μm);以甲醇-0.1%磷酸溶液(78∶22)为流动相;流速：1.0 mL·min^-1;柱温：30 ℃;检测波长：280 nm。结果 阿魏酸、芦丁、大黄酸、大黄素和大黄酚峰线性范围分别为0.020 82~0.416 3 μg·mL^-1(r=0.999 7),0.011 32~0.278 3 μg·mL^-1(r=0.999 3),0.017 22~0.344 3 μg·mL^-1(r=0.999 5),0.015 79~0.315 8 μg·mL^-1(r=0.999 6)和0.051 34~1.027 μg·mL^-1(r=0.999 9),平均加样回收率分别为97.4%(RSD=1.1%),95.0%(RSD=0.88%),97.5%(RSD=1.3%),97.4%(RSD=1.4%)和96.3%(RSD=0.87%)。结论 新建方法简便、准确,可用于黄石感冒片的定量分析方法。     

HPLC-ELSD同时测定跌打丸中三七皂苷R1、人参皂苷Rg1和人参皂苷Rb1的含量

目的 建立同时测定跌打丸中三七皂苷R₁、人参皂苷Rg₁和人参皂苷Rb1含量的HPLC-ELSD检测方法。方法 采用Phenomenex Kinetex C₁₈色谱柱(100 mm×4.6 mm,2.6 μm),柱温30 ℃,流速0.5 mL·min^-1,流动相为乙腈-水,梯度洗脱,ELSD检测器,漂移管温度110 ℃,载气(空气)体积流量3.0 L·min^-1。结果 三七皂苷R₁、人参皂苷Rg₁、人参皂苷Rb1分别在0.158~3.16 μg(r=0.999 8),0.407~8.14 μg(r=0.999 5),0.446~8.92 μg(r=0.999 9)内呈良好的线性关系,平均加样回收率分别为97.55%(RSD=1.04%),98.09%(RSD=1.03%),97.34%(RSD=0.81%)。结论 该方法简便、快速、准确,可用于跌打丸的质量控制。     

HPLC测定格列美脲有关物质的改进

目的 改进格列美脲有关物质检测的高效液相色谱法。方法 采用Agilent Zorbax SB-C₁₈色谱柱(250 mm×4.6 mm,5 μm),以磷酸二氢钠溶液(取0.5 g磷酸二氢钠,加水500 mL溶解,用磷酸调pH至2.5)-乙腈(50∶50)为流动相,流速1.0 mL· min^-1,检测波长为228 nm。结果 溶剂对杂质检测无影响,格列美脲与已知杂质分离度良好,杂质1与杂质2的定量限均为10 ng·mL^-1,杂质1在0.304 2~2.028 μg·mL^-1,杂质2在0.316 2~2.108 μg·mL^-1内呈良好线性关系(r分别为0.999 5和0.999 7),平均回收率分别为 100%和99%,RSD为1.4%和1.3%。结论 改进的方法消除了溶剂对杂质检测的干扰,可用于格列美脲中有关物质的检测。     

苯扎贝特纳米脂质载体的包封率测定

目的 建立苯扎贝特纳米脂质载体包封率的测定方法。方法 采用葡聚糖凝胶柱层析法分离苯扎贝特纳米脂质载体中的游离药物,高效液相色谱法测定其含量,计算包封率。色谱条件：采用Agilent ZORBAX SB-C₁₈柱(250 mm×4.6 mm,5 μm),流动相为0.01 mol·L^-1磷酸盐缓冲液(pH 3.0)-甲醇(30∶70),流速：1.0 mL·min^-1,检测波长：230 nm,进样量：20 μL。结果 苯扎贝特峰与杂质峰的分离度良好,苯扎贝特浓度在4.44~177.6 μg·mL^-1内与峰面积呈良好的线性关系(r=0.999 9),平均回收率为99.23%(RSD=0.68%)。3批苯扎贝特纳米脂质载体的包封率均>75%。结论 本方法简便、准确,灵敏度高,可用于苯扎贝特纳米脂质载体的质量控制。     

HPLC法同时测定复方三维右旋泛酸钙糖浆中4中维生素的含量

目的 建立高效液相色谱(HPLC)法同时测定复方三维右旋泛酸钙糖浆中维生素B₁、维生素B₂、维生素B₆和烟酰胺的含量。方法 采用外标法进行测定,色谱柱为Thermo Betasil C₁₈ Analytical(4.6 mm×250 mm, 5 μm),流动相为乙腈-5 mmol·L^-1十二烷基硫酸钠（含0.05%甲酸）水溶液梯度洗脱,流速1.0 mL·min^-1,检测波长260 nm,柱温30 ℃。分别测定10批复方三维右旋泛酸钙糖浆。结果 维生素B₁、维生素B₂、维生素B₆、烟酰胺4种成分的线性范围分别为5.76~115.2 μg·mL^-1(r=0.999 9)、1.16~23.20 μg·mL^-1(r=0.999 9)、1.72~34.4 μg·mL^-1(r=0.999 6)和5.76~115.2 μg·mL^-1(r=0.999 9),平均加样回收率为96.2%~98.4%(RSD为2.14%~3.42%)。不同批次复方三维右旋泛酸钙糖浆中维生素B₁、维生素B₂、维生素B₆、烟酰胺含量范围分别为0.133 7~0.155 9、0.027 86~0.030 71、0.039 05~0.047 7、0.138 7~0.148 2 mg·g^-1。结论 该方法为完善复方三维右旋泛酸钙糖浆的质量标准和加强质量控制提供了新的方法和依据。     

HPCE与HPLC测定科博肽注射液含量的方法比较

目的 系统地比较高效毛细管电泳法(HPCE)和高效液相色谱法(HPLC)在测定科博肽注射液含量方面的差异。方法HPCE分离条件为：未涂层毛细管柱(50 μm×40 cm,有效长度30 cm),运行缓冲液为0.1 mol·L^-1磷酸盐缓冲液(pH 2.5),分离电压20 kV,柱温25 ℃,检测波长200 nm;HPLC分离条件为：Aeris PEPTIDE XB-C₁₈柱(4.6 mm×150 mm,3.6 μm),柱温30 ℃,流速0.9 mL·min^-1,检测波长200 nm,流动相A：0.1%三氟乙酸-水、流动相B：0.1%三氟乙酸-乙腈,梯度洗脱。结果 科博肽在HPLC和HPCE各自的分离条件下进样浓度分别在17.33~138.60 μg·mL^-11、1.08~138.60 μg·mL^-1内表现出良好的线性关系(r均为0.999 7),平均加样加收率分别为100.3%和99.3%,RSD 分别为0.7%和1.2%。结论 HPCE与HPLC均可用于科博肽注射液的含量测定,但HPCE在使用成本、分离时间、检出限等方面更具有优势。     

HPLC测定三七提取液中三七皂苷R2(S)、七叶胆苷XVII和人参皂苷F2的含量

目的 建立同时测定三七提取液中三七皂苷R₂(S)、七叶胆苷XVII及人参皂苷F₂含量的高效液相色谱法。方法 色谱柱为Waters Acquity UPLC CSH-C₁₈(50 mm×2.1 mm,1.7 μm),流动相为0.01%甲酸-水(A)和0.01%甲酸-乙腈(B),梯度洗脱,检测波长为203 nm,进样量为5 μL,流速为0.35 mL·min^-1,柱温为40 ℃。结果 在43 min内可完成三七皂苷R₂(S)、七叶胆苷XVII和人参皂苷F₂的分离测定。3种皂苷峰面积和浓度线性关系良好(r²>0.999 8);日内和日间精密度RSD<3.4%;回收率为98.4%~102.1%。结论 该方法简便、准确,重复性好,可用于三七提取液中皂苷成分的测定。     

HPLC法测定布洛伪麻缓释片的释放量

摘 要 目的:建立高效液相色谱法测定布洛伪麻缓释片释放量的方法。方法: 色谱柱为迪马 C₁₈（250 mm×4.6 mm,5 μm）,流动相为甲醇-三乙胺-0.04 mol·L^-1 磷酸二氢钠溶液 (60∶0.02∶40),流速为1.0 ml·min^-1,检测波长为215 nm,柱温为35℃,进样量为20 μl。结果:布洛芬的线性范围为40～2 000 μg·mL^-1（r＝1.000 0）,平均加样回收率为99.2％,RSD＝0.8％(n=9),最低定量浓度为0.04μg· mL^-1;盐酸伪麻黄碱的线性范围为6～300 μg·mL^-1（r＝1.000 0）,平均加样回收率为98.5％,RSD＝0.6％(n=9),最低定量浓度为0.06μg· mL^-1。结论: 该方法简便快速、准确灵敏,可用于布洛伪麻缓释片释放量的测定。     

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.     

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.