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Direct Quantitation of D-serine in Human Plasma by Enantioselective Liquid Chromatography with Tandem Mass Spectrometry and its Application to a Clinical Study 对映选择液相色谱-串联质谱法直接定量人血浆中d -丝氨酸及其在临床研究中的应用
Pub Date : 2019-04-15 DOI: 10.17145/JAB.19.005
Estela Skende, Lei Shi, N. Zheng, Yu-Luan Chen
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引用次数: 0
Meet our Editorial Board Member: Dr. Xiaobin Xu 见见我们的编辑委员会成员:许晓斌博士
Pub Date : 2019-04-15 DOI: 10.17145/JAB.19.004
Xiaobin Xu
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引用次数: 0
Trends in Sample Preparation for the HPLC Determination of Penicillins in Biofluids 高效液相色谱法测定生物体液中青霉素类药物样品制备的发展趋势
Pub Date : 2019-01-31 DOI: 10.17145/JAB.19.003
V. Alampanos, V. Samanidou, I. Papadoyannis
INTRODUCTION Penicillins constitute a category of bicyclic organic compounds which are characterized by the presence of a β-lactam ring fused with a thiazoline ring, as shown in Figure 1. They appear to be highly effective against bacterial infections. Therefore antibiotics are extensively used by humans and animals by ingestion. These drugs inhibits the enzymes involved in the biosynthesis of the peptidoglycan in the cell wall. the enzymes involved in the biosynthesis of the peptidoglycan in the cell wall. Penicillins are classified, based on the mode of their activity, or according to their efficacy against bacterial β-lactamases, so they can be used as narrow-spectrum antibiotics. There is constantly a great interest for the quantitative determination of penicillins in biofluids for various reasons as for example, the knowledge of the time above the minimum inhibitory concentration (t > MIC) the most determinant ABSTRACT: Penicillin antibiotics are widely used for antibacterial treatment. Quantitative determination of these drugs in bio-fluids is constantly under a great need. HPLC is the more common analytical technique for this purpose. During the last decades, Green Analytical Chemistry is on the rise and is proven a new tendency. Sample preparation, as a crucial step of the analytical procedure, is strongly affected and determined by this new scientific perspective. Therefore, a variety of new microextraction techniques have been developed, which can be combined with the chromatographic determination of biofluids. In this review, current trends and methods of sample preparation are presented, which are appropriate to be used in order to extract penicillin antibiotics from biological samples prior to their HPLC separation. These methods are compatible with the principles of green analytical chemistry, which is an extreme necessity of our era, for both environmental and economic reasons. The evolution and establishment of these microextraction analytical techniques for sample preparation constitute a significant field of modern research due to their importance in the whole analytical procedure. Bioanalytical applications are set in the spotlight.
青霉素是一类双环有机化合物,其特征是β-内酰胺环与噻唑啉环融合,如图1所示。它们似乎对细菌感染非常有效。因此,抗生素被人类和动物广泛使用。这些药物抑制细胞壁中参与肽聚糖生物合成的酶。肽酶参与细胞壁中肽聚糖生物合成的酶青霉素根据其活性模式或对细菌β-内酰胺酶的功效进行分类,因此它们可作为窄谱抗生素使用。摘要:青霉素类抗生素被广泛应用于抗菌药物的治疗中,对生物体液中青霉素类抗生素的定量测定一直是人们关注的热点。生物体液中这些药物的定量测定一直是一个很大的需求。高效液相色谱法是用于此目的的更常用的分析技术。在过去的几十年里,绿色分析化学正在兴起,并被证明是一种新的趋势。样品制备作为分析过程的关键步骤,受到这种新的科学观点的强烈影响和决定。因此,各种新的微萃取技术被开发出来,它们可以与生物流体的色谱测定相结合。本文综述了生物样品HPLC分离前提取青霉素类抗生素的最新趋势和制备方法。这些方法符合绿色分析化学的原则,这是我们这个时代的极端需要,无论是环境还是经济原因。由于这些微萃取分析技术在整个分析过程中的重要性,它们的发展和建立构成了现代研究的一个重要领域。生物分析的应用备受关注。
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引用次数: 11
Meet our Editorial Board Member: Dr. Kai Wang 这是我们的编委会成员:王凯博士
Pub Date : 2019-01-30 DOI: 10.17145/jab.19.002
Kai Wang
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引用次数: 0
Determination of Ganciclovir and Acyclovir in Human Serum using Liquid Chromatography-Tandem Mass Spectrometry 液相色谱-串联质谱法测定人血清中更昔洛韦和阿昔洛韦的含量
Pub Date : 2018-12-31 DOI: 10.17145/JAB.18.022
A. Märtson, K. V. Hateren, G. Bosch, T. Werf, D. Touw, J. Alffenaar
Abstract OBJECTIVES: Currently there is no data about a liquid chromatography tandem mass spectrometry (LC-MS/MS) assay including ganciclovir and acyclovir using stable-isotopically labeled internal standards. METHODS: LC-MS/MS assay for measurement of ganciclovir and acyclovir using deuterated standards: ganciclovir-[2H5] and acyclovir-[2H4] was developed. The selectivity and sensitivity, linearity, accuracy and precision, recovery, matrix effect, stability, total process efficiency, carry-over and dilution integrity were validated based on EMA and FDA guidelines. RESULTS: The retention time for ganciclovir was 1.1 min and for acyclovir 1.35 min. Calibration curves were linear over a range of 0.1 to 20 mg/L and the correlation coefficient (R2) was 0.99912 for ganciclovir and 0.99945 for acyclovir. The calculated accuracy was –2.0% to 3.1% for ganciclovir and –1.0% to 6.4% for acyclovir. Within-day precision ranged from 1.8% to 6.6% for ganciclovir and 1.6 % to 6.5% for acyclovir and between-day precision 0% to 9.6% for ganciclovir and 0% to 7.9% for acyclovir. CONCLUSIONS: A rapid and validated LC-MS/MS method was developed for measurement of ganciclovir and acyclovir in human serum which can be used in routine patient care and clinical research.
目的:目前还没有液相色谱串联质谱(LC-MS/MS)检测更昔洛韦和阿昔洛韦的数据,该方法使用稳定同位素标记的内标。方法:采用更昔洛韦-[2H5]和阿昔洛韦-[2H4]的氘化标准物,建立了更昔洛韦和阿昔洛韦的LC-MS/MS检测方法。根据EMA和FDA指南验证了选择性和灵敏度、线性度、准确度和精密度、回收率、基质效应、稳定性、总工艺效率、结转和稀释完整性。结果:更昔洛韦的保留时间为1.1 min,阿昔洛韦的保留时间为1.35 min。在0.1 ~ 20 mg/L范围内,更昔洛韦和阿昔洛韦的相关系数(R2)分别为0.99912和0.99945。更昔洛韦的计算准确度为-2.0% ~ 3.1%,阿昔洛韦的计算准确度为-1.0% ~ 6.4%。更昔洛韦的日内精密度为1.8% ~ 6.6%,阿昔洛韦的日内精密度为1.6% ~ 6.5%,更昔洛韦的日内精密度为0% ~ 9.6%,阿昔洛韦的日内精密度为0% ~ 7.9%。结论:建立了一种快速、有效的LC-MS/MS测定人血清中更昔洛韦和阿昔洛韦含量的方法,可用于常规患者护理和临床研究。
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引用次数: 6
Liquid Chromatography-Tandem Mass Spectrometry Assays for Therapeutic Drug Monitoring of Cefepime 液相色谱-串联质谱法监测头孢吡肟的治疗药物
Pub Date : 2018-12-31 DOI: 10.17145/JAB.18.019
G. Moorthy, K. Downes, Nicole R. Zane, A. Zuppa
Competing interests: The authors have declared that competing interest exist. 1Center for Clinical Pharmacology, Children’s Hospital of Philadelphia, Philadelphia, USA. 2Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia, Philadelphia, USA. 3Division of Infectious Diseases, Children’s Hospital of Philadelphia, Philadelphia, USA. 4Department of Pediatrics, Children’s Hospital of Philadelphia, and Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
利益竞争:作者宣称存在利益竞争。1费城儿童医院临床药理学中心,美国费城;2费城儿童医院麻醉与重症医学科,美国费城;3费城儿童医院传染病科,美国费城;4费城儿童医院儿科,美国费城宾夕法尼亚大学佩雷尔曼医学院。
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引用次数: 1
Determination of Flucytosine in Human Serum using Liquid Chromatography-Tandem Mass Spectrometry 液相色谱-串联质谱法测定人血清中氟胞嘧啶
Pub Date : 2018-12-31 DOI: 10.17145/jab.18.020
J. Alffenaar, K. V. Hateren, D. Touw
OBJECTIVES: Flucytosine is an important drug for the combination treatment of cryptococcal meningitis in patients suffering from an infection with human immunodeficiency virus. As new synergistic regimens are being explored in clinical trials a full oral regimen may be near. For such a study evaluation of drug exposure is of critical importance as bioavailability could be compromised and elimination highly depends on renal function. No simple LC-MS/MS method for therapeutic drug monitoring of flucytosine has been published.
目的:氟胞嘧啶是联合治疗人类免疫缺陷病毒感染的隐球菌性脑膜炎的重要药物。随着新的协同方案正在临床试验中探索,一个完整的口服方案可能很快就会出现。对于这样的研究,评估药物暴露是至关重要的,因为生物利用度可能受到损害,消除高度依赖于肾功能。目前尚无简单的LC-MS/MS方法用于氟胞嘧啶治疗药物监测。
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引用次数: 2
Making a Difference in Therapeutic Drug Monitoring of Antimicrobial Drugs; the Need for LC-MS/MS 在抗菌药物治疗药物监测中有所作为LC-MS/MS的必要性
Pub Date : 2018-12-31 DOI: 10.17145/jab.18.018
J. Alffenaar, D. Touw
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引用次数: 0
Therapeutic Drug Monitoring of Protein Unbound Ciprofloxacin Concentrations to avoid inadequate Treatment of severe Bacterial Infections in Critically ill Patients 治疗药物监测蛋白未结合环丙沙星浓度避免危重病人严重细菌感染治疗不足
Pub Date : 2018-12-31 DOI: 10.17145/JAB.18.021
Noortje J D Mabelis, Kimberly N. Shudofsky, J. J. V. Raaij, S. Meenks, T. Havenith, S. Croes, J. L. L. Noble, P. Janssen
OBJECTIVES: To develop a reliable ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for therapeutic drug monitoring (TDM) of unbound ciprofloxacin concentrations in critically ill patients. METHODS: Total and unbound ciprofloxacin concentrations of five randomly selected intensive care unit (ICU) patients were measured using UPLC-MS/MS. Method validation included accuracy, linearity, precision, repeatability, and limits of detection and quantification. RESULTS: The median unbound ciprofloxacin fraction was 74.8%, with a median area under the curve from 0-24 h (AUC0-24) and maximum serum concentration (Cmax) of 28.51 h·mg/L and 4.45 mg/L respectively. Median free AUC0-24 (fAUC0-24) and free Cmax (fCmax) were 21.57 h·mg/L and 3.53 mg/L respectively; 20% of patients reached the pharmacodynamic target. The UPLC-MS/ MS method was validated using an intra-assay and inter-assay precision < 3%. Recoveries were between 90-110% CONCLUSIONS: This UPLC-MS/MS method provided reliable unbound ciprofloxacin concentrations, allowing target attainment in critically ill patients and exploration of different dosing regimens.
目的:建立一种可靠的超高效液相色谱-串联质谱(UPLC-MS/MS)监测危重患者非结合环丙沙星治疗药物浓度(TDM)方法。方法:随机选择5例重症监护病房(ICU)患者,采用超高效液相色谱-质谱联用仪(UPLC-MS/MS)测定其环丙沙星总浓度和非结合浓度。方法验证包括准确性、线性度、精密度、重复性、检测限和定量限。结果:环丙沙星游离分数中位数为74.8%,0 ~ 24 h曲线下面积中位数(auc0 ~ 24),最大血药浓度(Cmax)分别为28.51 h·mg/L和4.45 mg/L。中位游离AUC0-24 (fAUC0-24)和游离Cmax (fCmax)分别为21.57 h·mg/L和3.53 mg/L;20%的患者达到药效学指标。UPLC-MS/ MS方法的分析内和分析间精密度< 3%。结论:该UPLC-MS/MS方法可提供可靠的非结合环丙沙星浓度,可达到危重患者的目标,并可探索不同给药方案。
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引用次数: 1
AFFINImeter Software: from its Beginnings to Future Trends- A Literature review AFFINImeter软件:从开始到未来趋势-文献综述
Pub Date : 2018-10-15 DOI: 10.17145/JAB.18.017
E. Vegas Muñoz, Ángel Piñeiro
INTRODUCTION Molecular recognition is one of the most important events in biological systems. The characterization of molecular interactions is a fascinating research area, fundamental to understand the function of biomolecules and to develop new bioactive compounds (drugs). The comprehensive thermodynamic and kinetic characterization of a binding event requires monitoring the formation of the complex(es) as a function of the concentration of reactants or as a function of time, and the subsequent data analysis using a mathematical model that describes the binding process monitored. During the past years, the growing interest in the field of molecular recognition has been reflected in a considerable improvement in the instruments sensitivity of well stablished biophysical techniques and in the development of new ones; yet less has been investigated in the development and optimization of new analysis tools for a reliable understanding of binding data, and here is where the software AFFINImeter has stepped in. AFFINImeter [1] is a shareware software for the general analysis of binding experiments. It was born upon the need of a tool for the analysis of isothermal titration calorimetry (ITC) measurements that could handle complex interactions in an easyto-use way. Since it was released as a cloud-based software in 2015 many scientist from academic labs, research institutes and pharmaceutical companies are being benefited from the advanced tools that AFFINImeter offers for the reliable characterization of interactions by ITC; at present, AFFINImeter has been adapted for the analysis of titration data generated from different biophysical techniques popular in drug design and discovery programs such as nuclear magnetic resonance (NMR), general spectrometric methods or Microscale thermophoresis (MST).
分子识别是生物系统中最重要的事件之一。分子相互作用的表征是一个迷人的研究领域,是理解生物分子功能和开发新的生物活性化合物(药物)的基础。结合事件的综合热力学和动力学表征需要监测络合物的形成作为反应物浓度的函数或作为时间的函数,并使用描述被监测的结合过程的数学模型进行后续数据分析。在过去几年中,对分子识别领域日益增长的兴趣反映在已建立的生物物理技术的仪器灵敏度和新技术的开发方面有了相当大的提高;然而,在开发和优化新的分析工具以可靠地理解绑定数据方面进行的研究却很少,这就是AFFINImeter软件介入的地方。AFFINImeter[1]是一款用于结合实验综合分析的共享软件。它诞生于对等温滴定量热法(ITC)测量分析工具的需求,该工具可以以易于使用的方式处理复杂的相互作用。自2015年作为基于云的软件发布以来,来自学术实验室、研究机构和制药公司的许多科学家都受益于AFFINImeter提供的先进工具,这些工具可以可靠地表征ITC的相互作用;目前,AFFINImeter已适用于分析药物设计和发现程序中流行的不同生物物理技术产生的滴定数据,如核磁共振(NMR),一般光谱法或微尺度热电泳(MST)。
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引用次数: 12
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Journal of Applied Bioanalysis
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