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.     

Determination of gemifloxacin on dried blood spots by hydrophilic interaction liquid chromatography with fluorescence detector: application to pharmacokinetics in rats

A highly selective, sensitive and rapid hydrophilic liquid interaction chromatographic method was developed and validated for determination of gemifloxacin on dried blood spots. The chromatographic separation was achieved on a reversed‐phase zwitterionic hydrophilic interaction liquid chromatographic ZIC®HILIC‐C₁₈ (4.6 × 100 mm; 5 µm) column using acetonitrile–10 mM ammonium acetate (pH 3.5; 80:20, v/v) as a mobile phase in an isocratic elution mode at a flow rate 0.6 mL/min at 27 °C. An on‐line fluorescence detector set at excitation and emission wavelengths of 269 and 393 nm, respectively was used for monitoring column eluents. Ciprofloxacin was used as an internal standard. The method was validated for accuracy, precision, linearity and selectivity by design of experiments following ICH guidelines. The assay exhibited a linear range of 25–5000 ng/mL for gemifloxacin on dried blood spots. The lower limit of detection was found to be 10 ng/mL. The intra‐ and inter‐assay coefficients of variation did not exceed 7.4% deviation of the nominal concentration. The recovery of GFX from dried blood spots was >95.0% and its stability was excellent with no evidence of degradation during sample processing for at least 3 months storage in a freezer at ?20 °C. Copyright © 2012 John Wiley & Sons, Ltd.     

增大夏克-哈特曼波前传感器动态范围的算法研究

为了保证夏克-哈特曼波前传感器具有高灵敏度的同时又具有较大的动态范围,提出了一种能够有效增大传感器动态范围的数据处理方法光斑归位法。该方法使不规则的光斑回归到各自原来的位置,形成一个规则的光斑阵列,找到光斑阵列中某个光斑与微透镜的匹配关系,进而找到所有的光斑与微透镜的匹配关系。该方法的优点在于光斑不需要被限制在子孔径内且在不增加硬件等其他辅助条件下能够有效地增大夏克-哈特曼波前传感器的动态范围。实验验证了光斑归位法的正确性和可行性,结果表明,光斑归位法是正确的且采用该方法的动态范围比传统算法的动态范围提高了25倍以上。     

Rapid assays of clozapine and its metabolites in dried blood spots by liquid chromatography and microextraction by packed sorbent procedure

A novel analytical approach has been developed for the determination of clozapine and its metabolites in dried blood spots on filter paper, using a chromatographic method coupled with a microextraction by packed sorbent procedure. The analytes were separated on a RP-C18 column using a mobile phase composed of 20% methanol, 16% acetonitrile and 64% aqueous phosphate buffer. Coulometric detection was used, setting the guard cell at +0.050 V, the first analytical cell at -0.200 V and the second analytical cell at +0.500 V. Clozapine and its metabolites were extracted from dried blood spots with phosphate buffer and, then, a microextraction by packed sorbent procedure for the sample clean-up was implemented obtaining good extraction yields. The calibration curve was linear over the 2.5-1000 ng mL(-1) blood concentration ranges for all the analytes. The method validation gave satisfactory results in terms of sensitivity, precision, selectivity and accuracy. The analytical method was successfully applied to dried blood spots from several psychiatric patients for therapeutic drug monitoring purpose.     

Turbulent spots in boundary layers in a free-piston shock-tunnel flow

In this paper, experiments to detect turbulent spots in the transitional boundary layers, formed on a flat plate in a free-piston shock tunnel flow, are reported. Experiments indicate that thin-film heat-transfer gauges are suitable for identifying turbulent-spot activity and can be used to identify parameters such as the convection rate of spots and the intermittency of turbulence.     

基于遗传算法的公交智能调度与优化——以南岳衡山景区为例

南岳衡山(以下简称南岳)以“外秀于林,内秀于文”驰名中外,作为风景名胜区近几年游客人数不断攀升。本文利用遗传算法对景区内公交线路的调度模型进行求解。首先,根据景区现有的公共交通资源和旅客的出行规律,构建了以旅游公交营运成本、游客等待成本和游客流失成本三方面优化目标的模型;然后,使用线性加权方法实现对旅客与营运公司双方利益兼顾,进一步完善模型;最后,利用Matlab对实地调研数据的车辆调度方案求解。表明该模型改善了南岳景区旅游交通,满足游客的合理需求,提升了旅游公司经营策略,真正成为“寿岳独秀”的知名品牌。     

The auto-measurement of the gap of LCD glass plates using sub-pixel accuracy estimation

In this paper, the distance between laser spots has been measured using sub-pixel accuracy estimation and the accuracy has been tested in a noise environment. Here, the correlation like method (CLM) is used for the distance measurement between two laser spots and to count the estimation precision effect under noise factor by relevant CLM theorems. From the maximum value of the data series, then the position of the center of laser spot can be derived by interpolation. The estimation precision effect under noise factor and DC offset are tested and analyzed by a computer system. Also, for improving the estimation precision, a Kalman filter, which is often applied for random estimation and control theorem, is adopted. The innovation research combines CLM, and Kalman filter in sub-pixel accuracy estimation is more precise. This method can be used for measuring the gap of LCD glass plates, of optical strain gauge and the characteristics of spectral, quickly and can be automated.     

Advanced aspects of electromagnetic SERS enhancement factors at a hot spot

In this paper, we discuss some advanced theoretical aspects of electromagnetic enhancement factors (EFs) in surface‐enhanced Raman scattering (SERS). We focus in particular on the influence of surface selection rules (SSRs) on SERS EFs at hot spots, and the determination of SERS depolarization ratios. Both aspects could be viewed as secondary (compared to the overall magnitude of the SERS EF), but are nevertheless observable experimentally and crucial for a fundamental understanding of SERS. They also share the property that they cannot be studied within the commonly used |E | ⁴ approximation to the SERS EFs, and appropriate tools are developed here to make predictions beyond this approximation in the case of a SERS hot spot. In addition, theoretical estimates of different types of (previously defined) EFs are provided, and their origins discussed for the typical example of a SERS substrate dominated by SERS hot spots. Finally, experimental measurements of SERS depolarization ratios are presented to support the theoretical predictions. Copyright © 2008 John Wiley & Sons, Ltd.     

Quantitative estimation of substances spotted on filter paper by photoacoustic spectroscopy

Quantitative estimation of coloured as well as colourless substances spotted on filter paper has been carried out by means of photoacoustic spectroscopy. The technique should be specially useful in the estimation of biological substances. Contribution No. 378 from the Solid State and Structural Chemistry Unit