Microextraction techniques in antibiotic monitoring in body fluids: Recent trends and future

The analysis of drugs in biomedical discipline targets a broad range of aims such as therapeutic drug monitoring, pharmacokinetic study to investigate the drug bioavailability, bioequivalence tests to evaluate the effect of formulation parameters, toxicology, and forensic science. Because of the low levels of typical antibiotics in plasma, blood, urine, exhalation samples, and other biological fluids as well as complex matrix of biological media, adequate sample preparation methods should be implemented for quantification of antibiotics. In this review, developments in well-established microextraction techniques for the clinical analysis of biological samples will be reviewed and discussed. This article presents an overview of microextraction methods for biological samples, focusing especially on antibiotics.     

高校物流公司联盟服务站选址的研究

以国内高校周边物流公司的现状入手,论述高校设立物流公司联盟服务站的特点和优势,提出高校物流公司联盟服务站设计程序.基于离散选址模型及其对高校物流联盟服务站选址模型的启示,给出高校物流公司联盟服务站选址的计算模型.最后,以某高校为例进行物流公司联盟服务站选址规划并与该校物流联盟服务站实际地址作比较,比较结果表明,选址计算法是一个有效的算法,可以很好地应用在高校物流公司联盟服务站选址的研究中.     

提升高职学院核心竞争力的战略思考

核心竞争力是高职学院持续竞争优势的源泉,是优秀高职学院的功能属性。从战略管理的视角,围绕高职学院核心竞争力的构成要素,阐述了提升高职学院核心竞争力的战略构想。     

A high-throughput liquid chromatography-tandem mass spectrometry method for simultaneous determination of direct oral anticoagulants in human plasma

Direct oral anticoagulants are widely used in many indications to prevent thromboembolic events. Routine therapeutic monitoring is not required; however, there is increasing evidence suggesting the benefit of plasma level measurement in some situations. In addition, laboratory monitoring might help improve patient and drug non-compliance and thus individualize therapy. In the present study, we developed a sensitive and high throughput ultra-high-performance liquid chromatography-tandem mass spectrometry method for simultaneous quantification of apixaban, dabigatran, edoxaban, and rivaroxaban in human plasma. A one-step extraction procedure in 96-well formate for phospholipid and protein removal was used for sample pre-treatment, and analytes were separated using gradient elution over 4.2 min. Analytes were detected on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring mode. The method was validated according to the European Medicine Agency guideline for the selectivity, linearity, and lower limit of detection, precision and accuracy, matrix effects, extraction recovery, carryover, dilution integrity, and stability over a concentration range of 3.0–1000 ng/ml for all analytes. The validated method was applied to real clinical samples of patients treated with one of the drugs. Therefore, we can conclude that our method is suitable for therapeutic drug monitoring of direct oral anticoagulants.     

Determination of selected phenothiazines in human plasma by solid-phase extraction and liquid chromatography with coulometric detection

A new analytical method, based on liquid chromatography with coulometric detection, has been developed and applied to the determination of selected phenothiazines (chlorpromazine, promazine, fluphenazine and levomepromazine) in human plasma. The drugs were separated on a Discovery pentafluorophenylpropyl column, using a mobile phase composed of acetonitrile (32%) and a pH 1.9 phosphate buffer (68%). Promethazine was used as the internal standard. Detection was carried out at an oxidation potential of +0.500 V. A novel clean-up procedure was developed by means of solid-phase extraction, using cyanopropyl cartridges, which gave good extraction yield for all the analytes, with absolute recovery values higher than 91.0%. The detector response was linear over a plasma concentration range of 0.5-250.0 ng mL⁻¹ for chlorpromazine, promazine and levomepromazine and of 0.2-4.0 ng mL⁻¹ for fluphenazine. Precision results, expressed by the intra-day and the inter-day relative standard deviation values, were good, being lower than 3.9%. Accuracy data were satisfactory as well.The method has been successfully applied to the analysis of drug plasma levels of psychiatric patients undergoing therapy with selected phenothiazines.     

太原市产业集群技术联盟试点初探

分析了太原市现有10个产业集群技术联盟所存在的问题,结合实际情况,提出了太原市产业集群技术联盟应侧重建设和完善的有效路径。     

Method development and validation for the quantification of dasatinib,erlotinib, gefitinib,imatinib, lapatinib,nilotinib, sorafenib and sunitinib in human plasma by liquid chromatography coupled with tandem mass spectrometry

To support pharmacokinetic‐guided dosing in individual patients, a fast and accurate method for simultaneous determination of anticancer tyrosine kinase inhibitors (TKIs) dasatinib, erlotinib, gefitinib, imatinib, lapatinib, nilotinib, sorafenib and sunitinib in human plasma was developed using high‐performance liquid chromatography and detection with tandem mass spectrometry (HPLC‐MS/MS). Stable isotopically labeled compounds of the eight different TKIs were used as internal standards. Plasma proteins were precipitated and an aliquot of supernatant was directly injected onto a reversed phase chromatography system consisting of a Gemini C₁₈ column (50 × 2.0 mm i.d., 5.0 µm particle size) and then compounds were eluted with a gradient. The outlet of the column was connected to a triple quadrupole mass spectrometer with electrospray interface. Ions were detected in the positive multiple reaction monitoring mode. This method was validated over a linear range from 20.0 to 10,000 ng/mL for erlotinib, gefitinib, imatinib, lapatinib, nilotinib and sorafenib, and from 5.00 to 2500 ng/mL for dasatinib and sunitinib. Results from the validation study demonstrated good intra‐ and inter‐assay accuracy (<13.1%) and precision (10.0%) for all analytes. This method was successfully applied for routine therapeutic drug monitoring purposes in patients treated with the investigated TKIs. Copyright © 2012 John Wiley & Sons, Ltd.     

航线联盟下航空货运网络枢纽点选址问题研究

本文研究航空联盟下航空货运网络的枢纽点选址问题(HLP),基于枢纽点的数量及位置随机与容量的限制。首先引入航线联盟选择概率函数,确定不同航段上的航线自营运输或外包运输的概率;其次根据选址中心法则,以网络总成本最小化为目标,建立枢纽点选址模型;再次采用改进的免疫混沌遗传算法求解模型;最后,以顺丰航空公司案例进行实例分析。结果表明:1)本文改进的算法较免疫混沌遗传算法并与免疫遗传算法及CPLEX结果对比,发现本文设计的算法有较强的收敛性和计算速度,且计算结果与CPLEX求解器求解结果相差不大;2)枢纽点数量不确定时,枢纽点的位置多集中在东部城市;3)航空公司选择联盟环境可以大大降低运营成本,航空公司为提高自身利润,应考虑加入联盟,从而降低自身成本。     

A clinical assay for the measurement of milrinone in plasma by HPLC mass spectrometry

Milrinone is a bipyridine phosphodiesterase inhibitor with positive inotropic and vasodilatory effects. As interest in longer term use of intravenous therapy increases, it becomes essential to monitor its plasma concentration owing to a narrow therapeutic range, an increased half-life in renal failure and toxicity associated with high levels. A high-performance liquid chromatography (HPLC) method with mass (MS) detection using a triple quadrupole mass spectrometer is presented. The method was compared with the UV/HPLC method and validated according to current international guidelines. Coefficients of variation of less than 7.5% were obtained across the therapeutic range and 18.3% at 2.4 ng/mL, the lower limit of quantitation. Plasma from 13 cardiac surgery patients receiving standard intravenous doses of milrinone were measured. Eight patients achieved therapeutic milrinone levels within 3-4 h post start of infusion, one was borderline sub-therapeutic and four patients achieved levels that were above the upper limit of the therapeutic range and potentially toxic. This method offers high sensitivity, is rapid, easy to use and requires minimal amount of sample. We believe this method could become the reference procedure for clinical monitoring of milrinone and help to improve the safety of the use of this drug in patients with cardiac failure.