Ketamine and norketamine stability in whole blood at ambient and 4°C conditions

A study was implemented to describe the pharmacokinetics (PK) of ketamine (K) and its metabolite norketamine (NK) in critically ill adults. Conducting studies in these subjects is hindered by the immediate need to process and freeze samples obtained in a busy intensive care setting. The ability to store unprocessed samples at room temperature for an extended time period would overcome this barrier. Stability and blood to plasma partitioning of K and NK were investigated in whole blood for up to 120 h at room temperature and 4°C. Whole blood was spiked with K and NK (1000 ng/mL each). Blood samples were aliquoted at different time points (0–120 h), extracted and analyzed using a validated high‐performance liquid chromatography tandem mass spectrometry assay. The study demonstrated the stability of both K and NK in whole blood up to 120 h. These in vitro studies suggest that the concentrations of K and NK measured in the PK samples are reliable. The established stability results were successfully employed to investigate K and NK pharmacology studies in critically ill adults.     

Effects of Tao‐Hong‐Si‐Wu decoction on acute blood stasis in rats based on a LC‐Q/TOF‐MS metabolomics and network approach

A novel approach using metabolomics coupled with a metabolic network was used to investigate the effects of Tao‐Hong‐Si‐Wu decoction (THSWD) on the rat model of acute blood stasis syndrome. Acute blood stasis syndrome was induced by placing the rats in ice‐cold water following two injections with epinephrine. The hemorheological indicators [whole blood viscosity (WBV) and plasma viscosity (PV)] and the blood coagulation indicators [thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (FIB)] were detected. The nonparametric univariate method and multivariate statistical analysis were performed for determining the potential biomarkers. A correlation map was structured between biochemical indicators and hub metabolites to explain the effects mechanism of THSWD. After the administration of THSWD, the levels of WBV, PV, TT, APTT and FIB returned to levels observed in the control group. According to metabolomics coupled with metabolic network analysis, the intervention of THSWD in rats with acute blood stasis syndrome induced substantial and characteristic changes in their metabolic profiles. Fifteen metabolites were screened, which mainly involved 10 pathways and five hub metabolites, namely, l ‐glutamate, l ‐phenylalanine, N‐acylsphingosine, arachidonic acid and phosphatidate. The biochemical indicators and hub metabolites could be adjusted to close to normal levels by THSWD. Therefore, combining metabolomics and metabolic network helped to evaluate the effects of THSWD on acute blood stasis.     

青春期多囊卵巢综合征患者代谢综合征的患病特点

目的探索青春期多囊卵巢综合征（PCOS）患者代谢综合征（MS）患病特点。方法收集80例青春期PCOS患者MS患病率与肥胖、年龄、胰岛素抵抗和ApoB/ApoA1比值的关系。结果青春期PCOS患者MS患病率为12.50%，其中非肥胖患者MS和前代谢综合征阶段（pre-MS）患病率分别为0.00%和7.55%，低于肥胖患者的37.04%和33.33%；两组pre-MS患病率差异有统计学意义（P＜0.05）。13~15岁组MS患病率为6.67%，低于16~19岁组的13.85%（P＜0.05）；pre-MS患病率为20.00%，高于16~19岁组的15.38%。胰岛素抵抗型患者的MS和pre-MS患病率分别为33.33%和33.33%，高于非胰岛素抵抗型患者的6.45%和11.29%（P＜0.05），ApoB/ApoA1≥0.6的患者MS和pre-MS患病率分别为33.33%和16.67%，高于ApoB/ApoA1＜0.6的患者6.45%和16.13%（P＜0.05）。结论青春期PCOS患者的MS患病率以肥胖、胰岛素抵抗型、ApoB/ApoA1≥0.6者较高，其中13~15岁人群pre-MS患病率较高。     

A simple and cost‐effective HPLC‐UV method for the detection of levetiracetam in plasma/serum of patients with epilepsy

A simple, fast and cost‐effective method was developed and validated for the determination of levetiracetam (LEV) in plasma/serum of patients using high performance liquid chromatography (HPLC) with ultraviolet detection. The stability of LEV plasma/serum samples over time and in different blood collection tubes was evaluated. Serum/plasma samples were deproteinized by methanol spiked with the internal standard, gabapentin. HPLC was carried out on a Venusil XBP C₁₈, 250 × 4.6 mm, 5 μm column, at a flow rate of 1.0 mL/min and with mobile phase consisting of 50 mm potassium dihydrogen phosphate–acetonitrile at a pH of 5.5. The UV detector was set at 205 nm and 10 μL was injected. Total runtime was 15 min. Calibration curves were linear (correlation coefficient = 0.999) over a concentration range of 1–60 μg/mL. Relative standard deviation values for both the inter‐day and intra‐day precision and accuracy were <5% for the concentration range. The influence of different collection tubes and the effect of time on the stability of LEV was investigated. These factors may cause inaccuracies owing to drug–protein binding and interference in the matrix. This method is simple, fast, cost‐effective, reliable and accurate with minimal sample preparation for daily routine use in therapeutic drug monitoring.     

Well‐balanced discontinuous Galerkin method and finite volume WENO scheme based on hydrostatic reconstruction for blood flow model in arteries

The blood flow model in arteries admits the steady state solutions, for which the flux gradient is nonzero, and is exactly balanced by the source term. In this paper, by means of hydrostatic reconstruction, we construct a high order discontinuous Galerkin method, which exactly preserves the dead‐man steady state, which is characterized by a discharge equal to zero (analogue to hydrostatic equilibrium). Moreover, the method maintains genuine high order of accuracy. Subsequently, we apply the key idea to finite volume weighted essentially non‐oscillatory schemes and obtain a well‐balanced finite volume weighted essentially non‐oscillatory scheme. Extensive numerical experiments are performed to verify the well‐balanced property, high order accuracy, as well as good resolution for smooth and discontinuous solutions.     

Three new flavans in dragon's blood from Daemonorops draco

Three new flavans were isolated from chloroform extracts of dragon's blood from Daemonorops draco, together with eight known compounds. The structures of the new flavans were determined by 1D and 2D NMR spectroscopic analysis. These compounds are the first examples of 2-methoxyflavans from D. draco and regarded as derivatives of biogenetic intermediates from flavans to chalcones, which are characteristic of the dragon's blood.     

Mathematical modelling of the patent ductus arteriosus (PDA)

The heart is one of the most important and vital body organs, which is responsible for pumping blood to different body tissues. Abnormalities in each part of heart can lead to lack of proper blood circulation. The arterial duct is one of the most important parts of embryonic cycles which may provide the possibility of a relationship between the aorta and the pulmonary artery. The failure of this duct to close after birth causes the abnormality called patent ductus arteriosus (PDA). In this article, we propose a novel model for accurate simulation of PDA abnormality in the human heart. The model is obtained by exploiting the mathematical relation between hemodynamic parameters of heart, including pressure, blood, volume and flow. The proposed model is verified using clinical data.     

Automated high throughput analysis of antiretroviral drugs in dried blood spots

For therapeutic drug monitoring in remote settings, dried blood spots (DBS) are particularly advantageous, as blood sample collection and handling is uncomplicated. The aim of this study was to develop and validate an automated extraction method for the analysis of nevirapine, efavirenz and lopinavir in DBS samples. Automated extraction was performed with methanol : water (70 : 30 v /v ), using a DBS‐MS 500 autosampler coupled to a liquid chromatography tandem mass spectrometry system. The autosampler used digital images of each DBS to position the extraction head, sprayed 10 μl of internal standard onto each DBS and extracted a 4‐mm disc (Ø) from the centre of each spot by unilateral flow using 25‐μl extraction solvent. The analytes were baseline separated on a pentafluorophenyl column and analysed by using electrospray ionization with multiple reaction monitoring in positive polarity mode for nevirapine and lopinavir and in negative mode for efavirenz. The method was linear between 10 and 10 000 ng/ml for all analytes. Automated sample extraction resulted in consistent recoveries (nevirapine: 70 ± 6%, efavirenz: 63 ± 11% and lopinavir: 60 ± 10%) and matrix effects between different donors and concentration levels. Intra‐day and inter‐day accuracy and precision deviations were ≤15%. Manual and automated extractions of DBS samples collected within the framework of an adherence assessment study in rural Tanzania showed good agreements with deviations of less than 10%. Our study highlights that therapeutic drug monitoring samples obtained in the resource‐constrained setting of rural Africa can be reliably determined by automated extraction of DBS. Overall, automatization improved method sensitivity and facilitates analysis of large sample numbers. Copyright © 2017 John Wiley & Sons, Ltd.     

On the Preparation and Distribution of two S35-Labelled Hypoglycemic Agents

Two S³⁵-labelled hypoglycemic agents were prepared by the interaction of labelled sulphonamide and urea derivatives. The R values of the intermediates as well as the products wer determined and compared with tolbutamide. The purity of the products was checked by melting point determination, infrared spectrum, and radioactivity investigations. Localization of the separated products on the chromatograms was done by colour reaction, radioscaning, and radioautography. Distribution of the labelled drung in different tissues of rats was also carried out to prove the site of action of the drung and to show its accumulation. Counting of these tissues has been carried out by means of a liquid scintillation counter type Nuclear Chicago.