基于超高效液相色谱-四级杆飞行时间串联质谱和网络药理学的甘枣宁治疗非酒精性脂肪性肝病药效物质基础研究

目的 探究甘枣宁的主要活性成分,预测并验证其治疗非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)的主要物质基础.方法 采用超高效液相色谱-四级杆飞行时间串联质谱(UPLC-Q-TOF-MS/MS),明确甘枣宁水煎液的化学成分.采用网络药理学方法检索甘枣宁活性成分及其潜...     

“二神丸”中补骨脂、肉豆蔻炮制前后对脾肾阳虚泄泻大鼠血清代谢组学的影响

运用代谢组学的方法,研究"二神丸"中补骨脂、肉豆蔻炮制前后干预脾肾阳虚泄泻大鼠血清内源性代谢物的变化,筛选出与脾肾阳虚泄泻相关的差异代谢物,探讨与脾肾阳虚泄泻相关的代谢模式及"二神丸"中补骨脂、肉豆蔻炮制增效机制。检测分析各组SOD,MDA,应用GC-MS检测不同时段的大鼠血液代谢图谱,采用主成分分析(PCA)方法和偏最小二乘法判别分析方法(PLS-DA)分析,通过变量重要性投影(VIP)和t检验筛选潜在生物标志物。结果显示,"二神丸"能使SOD活性升高,MDA含量降低。确定了10个与脾肾阳虚泄泻相关的差异代谢物。与模型组比较,"二神丸"干预后代谢物水平不同程度回调,且"二神丸"Ⅳ组(盐炙补骨脂+麸煨肉豆蔻)效果最好,推测"二神丸"中补骨脂、肉豆蔻炮制增效可能从抑制过氧化、改善糖脂、氨基酸及能量代谢等多层面协同发挥作用,具有多靶点性。     

荧光分光光度法测定人尿中氟罗沙星的含量

目的:建立灵敏、准确、简便、快速的方法测定人尿中氟罗沙星的含量.方法:以290 nm为激发波长,以458 nm为发射波长,用荧光分光光度法测定人尿中氟罗沙星的排出速率.结果:氟罗沙星浓度在0.05～0.5 mg*L-1范围内,荧光强度与浓度呈良好的线性关系,检测限为0.03 mg*L-1.精密度为日内RSD<1.10%,日间RSD<2.98%(n=5),回收率为(98.6±1.3)%.结论:采用此法测定了2名健康受试者口服氟罗沙星片后的尿药排出速率.尿中药物排出速率最高是在服药后6～8 h,24 h内尿药累积排出率为56.12%,0～24 h内尿药浓度为(69.3±40.6)mg*L-1,显著高于大多数常见致病菌的MIC90,表明有效尿药浓度至少可维持24 h.     

儿童丙戊酸群体药动学

目的:研究仅有临床稀疏数据的儿童丙戊酸群体药动学.方法:收集667例儿童癫痫患者的常规治疗药物监测资料,将794对血药浓度-时间数据利用群体药动学理论经CPKDP程序处理,提取儿童群体药动学参数,再经Bayesian反馈法及二步迭代计算出儿童个体药动学参数.结果:儿童丙戊酸群体药动学主要参数Ke、Vm、CL在单用丙戊酸组分别为(4.5±2.2)h-1、(1.4±0.5)L·kg-1和(14.5±4.3)mL·h-1·kg-1;在合并其他抗癫痫药物时分别为(7.3±3.4)h-1、(1.4±0.6)L·kg-1、(24.8±9.3)mL·h-1·kg-1.预测浓度和实测浓度显著相关;合并PB、PTH、CBZ、CNP对丙戊酸的药动学有显著影响.结论:本研究对儿童丙戊酸给药方案个体化提供有价值的参考依据.     

Integral pharmacokinetics of multiple lignan components in normal, CCl4-induced hepatic injury and hepatoprotective agents pretreated rats and correlations with hepatic injury biomarkers

Although pharmacokinetic alternations by hepatic injury have been extensively studied, little is known about the potential influence of hepatoprotective agent's treatment. This study was aimed to investigate the holistic pharmacokinetics of multiple lignans, CYP3A regulations, and their correlations with hepatic injury biomarkers, in hepatic injured rats pretreated with or without schisandra lignan extract (SLE) and dimethyl-diphenyl-bicarboxylate (DDB). Integral pharmacokinetics of multiple lignans based on an AUC-weighting approach was determined in normal, CCl4 induced hepatic injury rats pretreated with or without SLE and DDB. Protein expression and activities of CYP3A were determined. Pharmacokinetic parameters and CYP3A activities were correlated with serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. CCl4 induced acute hepatic injury resulted in a nearly 8-fold enhancement of integral plasma exposures of multiple lignans, which was caused by the significant down-regulation of CYP3A. SLE and DDB pretreatment exhibited potent hepatoprotective effects, accompanied with the restored expression and activity of CYP3A, and the recovery of the respective and integral pharmacokinetics of lignans components. The integral AUC_0-tn and CYP3A activities correlated well with ALT and AST. This study suggested that the pharmacokinetic regulating effects of hepatoprotective agent's on themselves and co-prescribed drugs should be of concern, and hepatic injury biomarkers may serve as good predictors.     

超高效液相-质谱法测定降脂颗粒中6种活性成分的含量（英文）

目的：利用超高效液相-质谱法建立同时测定降脂颗粒中6种活性成分含量的方法。方法：色谱柱为Acquity UPLC BEH C18柱（2.1mm×50mm,1.7μm）,流动相为甲醇-0.1%甲酸水梯度洗脱,选择离子监测。结果：在线性范围内相关系数良好,均大于0.9992,日内、日间精密度良好,RSD值均小于3%,加样回收率在97.58%-103.12%,符合要求。结论：本方法快速灵敏,测定结果准确可靠,可用于降脂颗粒的质量控制。     

Pharmacokinetics of magnesium lithospermate B after intravenous administration in beagle dogs

AIM: To develop a specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the phar-macokinetic study of magnesium lithospermate B (MLB), and study the pharmacokinetics of MLB after iv administration in beagle dogs. METHODS: Each beagle dog was iv administered MLB 3, 6, and 12 mg/kg random. The serum drug concentration was determined by specific liquid chromatography-tandem mass spectrometry (LC-MS/ MS) assays. The pharmacokinetic parameters were calculated by Drug and Statistics version 1.0 program. RESULTS: The calibration curve for MLB was linear over a range of 16-4096μg/L with coefficients of correlation >0.999. The intra- and inter-day precisions (CV) of analysis were <10 %, and accuracy ranged from 90 % to 113 %. After iv administration of MLB at the doses of 3, 6, and 12 mg/kg, the C0 values for MLB were estimated to be of 24, 47, and 107 mg/L, respectively. The AUC increased with the increasing doses for iv administration, and the mean AUC0-t values were 109.3, 247.9, and 5     

氢化物发生-原子荧光光谱法测定锁阳中汞和砷的含量

目的: 建立氢化物发生-原子荧光光谱法测定锁阳药材中有害元素汞、砷的定量检测方法。 方法: 采用高氯酸-硝酸消解,原子荧光光谱法测定。 结果: 汞在0.1~0.5 ng ·mL^-1线性关系良好,回归方程Y=3.54×10²X+9.54,r=0.999 7,最低检出限为0.022 ng ·mL^-1;砷在1.0~10.0 ng ·mL^-1线性关系良好,回归方程Y=1.65×10²X-3.89,相关系数r=0.999 9,最低检出限为0.151 ng ·mL^-1。 结论: 该方法简便快速,结果准确可靠,结果满意,可为锁阳药材质量标准体系中有害成分的限量规定提供参考。     

液质联用技术研究肽类药物药动学中的样品制备技术

肽类药物的研究开发成为新生物技术药物研究开发的热点之一。然而，建立可靠、灵敏和准确的肽类药物体内分析方法是肽类药物临床前和临床药动学研究的难点。样品制备技术是建立符合药动学研究要求的定量分析方法的关键。现综述液质联用技术在肽类药物药动学研究中的样品制备技术方法的目的、要求、特点和分类。结合近年发表的文献具体阐述了固相萃取法、蛋白质沉淀法、超滤离心法、亲和层析法和部分其他方法的原理及其应用实例。     

Is there a risk of human poisoning by azaspiracids from shellfish harvested at the Portuguese coast?

Azaspiracid poisoning (AZP), the most recently discovered human gastrointestinal illness resulting from consumption of contaminated shellfish, so far has been found in coastal areas of northern Europe. This is the first report of a survey carried out for contamination of shellfish harvested in costal areas of Portugal for the presence of azaspiracids. The study design covered the commercial species usually more contaminated by toxins from dinoflagellates (blue mussel, common cockle, donax clam) in coastal areas representative of the NW, SW and south coasts. A method based on liquid chromatography–mass spectrometry was setup for the first time for this purpose. No azaspiracids were found on 300 samples tested between 2002 and 2003. On at least three samples a peak with a retention time matching that of AZA2 was found, never surpassing one tenth of the current EU limit. Unambiguous identification of any known AZA did not occur yet. The risk for human outbreaks of AZP seems to be very low, comparatively with amnesic shellfish poisoning (ASP), where levels close to the allowance level are found sparsely, or to diarrhetic shellfish poisoning (DSP) and paralytic shellfish poisoning (PSP), where high levels and registered human outbreaks have been found in recent years.