Salting‐out‐assisted liquid–liquid extraction with acetonitrile for the determination of trimetazidine in rat plasma using liquid chromatography–mass spectrometry

A high‐throughout bioanalytical method based on salting‐out‐assisted liquid/liquid extraction (SALLE) method with acetonitrile and mass spectrometry‐compatible salts followed by LC‐MS/MS analysis of trimetazidine in rat plasma is presented. It required only 50 μL of plasma and allows the use of minimal volumes of organic solvents. The seamless interface of SALLE and LC‐MS eliminated the drying‐down step and the extract was diluted and injected into an LC‐MS/MS system with a cycle time of 2.5 min/sample. The retention times of trimetazidine and IS were approximately 1.1 and 1.7 min, respectively. Calibration curves were linear over the concentration range of 0.1–100 ng/mL, which can be extended to 500 ng/mL by dilution. The intra‐ and inter‐batch precision, accuracy and the relative standard deviation were all <15%. This method was successfully applied to determine trimetazidine concentrations in rat plasma. Copyright © 2014 John Wiley & Sons, Ltd.     

Metabolic profiles of dioscin in rats revealed by ultra‐performance liquid chromatography quadrupole time‐of‐flight mass spectrometry

Dioscin (DIS), one of the most abundant bioactive steroidal saponins in Dioscorea sp., is used as a complementary medicine to treat coronary disease and angina pectoris in China. Although the pharmacological activities and pharmacokinetics of DIS have been well demonstrated, information regarding the final metabolic fates is very limited. This study investigated the in vivo metabolic profiles of DIS after oral administration by ultra‐performance liquid chromatography quadrupole time‐of‐flight mass spectrometry method. The structures of the metabolites were identified and tentatively characterized by means of comparing the molecular mass, retention time and fragmentation pattern of the analytes with those of the parent compound. A total of eight metabolites, including seven phase I and one phase II metabolites, were detected and tentatively identified for the first time. Oxidation, deglycosylation and glucuronidation were found to be the major metabolic processes of the compound in rats. In addition, a possible metabolic pathway on the biotransformation of DIS in vivo was proposed. This study provides valuable and new information on the metabolism of DIS, which will be helpful for further understanding its mechanism of action. Copyright © 2015 John Wiley & Sons, Ltd.     

A novel LC–MS/MS method for the determination of ziritaxestat in rat plasma and its pharmacokinetic study

Ziritaxestat is a first-in-class autotoxin inhibitor. The purpose of this study was to develop a liquid chromatography/electrospray ionization tandem mass spectrometric (LC–MS/MS) method for the determination of ziritaxestat in rat plasma. The plasma sample was deproteinated using acetonitrile and then separated on an Acquity BEH C₁₈ column with water containing 0.1% formic acid and acetonitrile as mobile phase, which was delivered at 0.4 ml/min. Ziritaxestat and the internal standard (crizotinib) were quantitatively monitored with precursor-to-product transitions of m/z 589.3 > 262.2 and m/z 450.1 > 260.2, respectively. The total running time was 2.5 min. The method showed excellent linearity over the concentration range 0.5–2000 ng/ml, with correlation coefficient >0.9987. The extraction recovery was >82.09% and the matrix effect was not significant. Inter- and intra-day precisions (RSD) were <11.20% and accuracies were in the range of −8.50–7.45%. Ziritaxestat was demonstrated to be stable in rat plasma under the tested conditions. The validated LC–MS/MS method was successfully applied to study the pharmacokinetic profiles of ziritaxestat in rat plasma after intravenous and oral administration. Pharmacokinetic results demonstrated that ziritaxestat displayed a short half-life (~3 h) and low bioavailability (20.52%).     

基于ATMega128无纸记录仪系统的设计与实现

在介绍了ATMega128和无纸记录仪系统的基础上，提出了无纸记录仪系统用基于ATMega128单片机来实现的方法和过程。显示方式采用的是320×240点阵无字库蓝色背光的LCD显示，显示信息量多，而且显示界面美观；存储方式在延续以往的EEPROM存储方式的同时，采用标准接口的大容量SD卡。     

Altered protein synthesis in rat kidney cells exposed to semiconductor materials

It is thought that the extensive industrial use of arsenic, gallium and indium, which have applications as the materials for III–V semiconductors, will increase human exposure to these compounds in the near future. We have undertaken the development of new biological indicators for assessing exposure to these elements. Element-specific alterations in protein synthesis patterns were expected to occur following exposure to arsenic compounds. We examined alterations in protein synthesis in primary cultures of rat kidney proximal tubule epithelial cells by sodium arsenite, gallium chloride and indium chloride, utilizing two-dimensional gel electrophoresis. After incubation with the chemicals for 20 h, newly synthesized proteins were labeled with [³⁵S]methionine. A protein with a molecular weight (M_r) of 30 000 was markedly induced on exposure to 10 μM arsenite or 300 μM gallium chloride, and synthesis of proteins with M_r values of 85 000, 71 000, 65 000, 51 000, 38 000 and 28 000 were also increased by exposure to arsenite and gallium chloride. No significant changes were observed upon exposure to indium. Some of these increased proteins could be heat-shock proteins.     

Different acute effects of oral and intratracheal administration of disodium arsenate and gallium arsenide on heme synthesis in rats

The acute influences of arsenic compounds on the metabolism of porphyrins and heme in various organs of rats after oral or intratracheal administration of disodium arsenate (Na₂HAsO₄) and gallium arsenide (GaAs) were examined and compared. For the oral administration experiments, 21 or 84 mg of Na₂HAsO₄, or 2 or 4 g of GaAs, per cm³ saline per kg body weight of each animal was administered to Jcl: Wistar male rats and the organs were removed after exsanguination from the vein of the right axilla under anesthesia with ether, 16 h after administration. In the case of intratracheal administration, rats given 8.2 or 16.4 mg of Na₂HAsO₄, or 0.2 or 0.4 g GaAs per cm³ saline per kg body weight were examined under the same experimental conditions as for the administration route. Increase in the body weight of rats was suppressed after intratracheal administration of the two arsenic compounds. In these rats the hematocrit value increased significantly. These changes were not shown by the orally administered rats. Elevation in δ-aminolevulinate synthase (ALA-S, EC 2.3.1.37) activity in erythroblasts by Na₂HAsO₄ was much higher after intratracheal administration than after oral administration. Suppression in the activities of δ-aminolevulinate dehydratase (ALA-D, EC 4.2.1.24) and porphobilinogen deaminase (PBG-D, EC 4.3.1.8) in peripheral erythrocytes by Na₂HAsO₄ and GaAs were stronger by intratracheal administration than by the oral route. Influences of GaAs on the activity of PBG-D in rat liver were shown to be more effective by oral administration than by the intratracheal route. Oral administration of Na₂HAsO₄ and GaAs had a stronger suppression effect on the activities of ALA-D and PBG-D in rat kidney. It seems from these results that the different extents of the influence of arsenic compounds might depend on the routes of intake.     

Metallothionein as a biomarker for mercury in tissues of rat fed orally with cinnabar

Cinnabar, as one of the most widely used mineral drugs in traditional Chinese medicines, has been proven to have prominent curative effects in clinical use for more than 2000 years. But the safety and toxicity of the drug has been under constant debate in clinic usage. Metallothionein (MT) contains about 30% of cysteine in the molecule, and plays an important detoxification role against heavy metals. In this study, it was used as a biomarker to assess mercurial accumulation in rats fed orally with cinnabar. After feeding rats with cinnabar by gastric gavage at different dosages and at different times, the distribution of heavy metals (including mercury, copper and zinc) and MT was investigated among rat tissues, including liver, kidney, heart, brain, testis and blood. Metals and MT determinations were carried out using inductively coupled plasma mass spectrometry (ICP‐MS) and a modified mercury saturation assay technique respectively. The results indicated that mercury was easily accumulated in the tissues of rats exposed to cinnabar, especially in kidney. For example: at a feeding dosage of 5 g kg^?1 (bw) for 4 weeks, the mercury concentrations in kidney were 13, 8.7, 21.6 and 26 times those in liver, testis, brain and heart respectively; and at 2.5 g kg^?1 (bw) for 2 weeks, the mercury concentrations in kidney were 21, 2.1, 3 and 21 times those in liver, testis, brain and heart respectively. In addition, mercury in kidney and liver of all cinnabar groups was significantly higher than that of the control group (P < 0.01). A high positive correlation observed between MT concentrations and mercury levels in both liver and kidney (R² = 0.9299, P < 0.02 for liver; R² = 0.9923, P < 0.0008 for kidney) indicated that MT could be used as a biomarker for mercury in tissues. Copyright © 2004 John Wiley & Sons, Ltd.     

SD对壳模型: 偶偶Pt核低激发态性质

利用SD对壳模型讨论了偶偶Pt核低激发态的集体性质. 结果发现在该模型下, 利用一个仅含有3个参数的哈密顿量, 可以很好地再现偶偶Pt核低激发谱的集体性质.