有机化学实验邻苯二甲酸二丁酯制备的绿色化研究

以对甲苯磺酸（PTS）为催化剂,邻苯二甲酸酐和正丁醇为原料,微量实验合成邻苯二甲酸二丁酯。最佳反应条件为：邻苯二甲酸酐为0．02mol,丁醇、苯酐物质的量比为3：1,催化刑用量为原料邻苯二甲酸酐物质的量的1．5％。反应时间0．45h,回流反应下酯化率可达95．8％。反应时间短．催化剂用量少易分离。能够重复使用,酯化率高,不污染环境,符舍绿色化学原则。     

Coupled columns in bioanalytical work

The bioanalytical laboratory giving a service in the development of new drugs has to provide flexibility as well as routinely assay a large number of samples, preferably with automated procedures. Liquid chromatography with coupled columns can be most useful for this purpose, as exemplified in the present paper, where a coupled-column configuration, which has been used for automation, screening and method validation, is described.     

Assessing similarity in bioanalytical methods

Due to the comparative nature of a bioassay, the relative potency is usually used to describe the potency of a sample. Only when the two samples are similar can a valid and meaningful estimate of relative potency be obtained. Thus, assessing similarity is a crucial part in developing a bioanalytical method. The current commonly used approach for assessing similarity focuses on the response parameters, such as the slope in the linear case, using either a significance test or an equivalence test. The current direct evaluation of the response parameters ignores the information about the shape of the curve and the possible variance heterogeneity. To overcome this, we propose a method based on the idea of equivalence testing that compares the shapes of the curves directly. The new method first measures the difference of the response between the standard sample and the test sample at each of the concentration (dilution) levels and then determines whether the differences are consistent by comparing them to the equivalence limits. The benefits of the new method are investigated by a simulation study. LAY ABSTRACT: Due to the comparative nature of a bioassay, the relative potency is usually used to describe the potency of a sample. Only when the two samples are similar can a valid and meaningful estimate of relative potency be obtained. Thus, assessing similarity is a crucial part in developing a bioanalytical method. The current commonly used approach for assessing similarity focuses on the response parameters, such as the slope in the linear case, which have many drawbacks To overcome this, we propose a method based on the idea of equivalence test but comparing the shape of curve directly. The new method first measures the difference of the response between the standard sample and the test sample at each of the concentration (dilution) levels and then determines whether the differences are consistent by comparing them to the equivalence limit.     

Regulatory observations in bioanalytical determinations

The concept of measuring analytes in biological media is a long-established area of the quantitative sciences that is employed in many sectors. While academic research and R&D units of private firms have been in the forefront of developing complex methodologies, it is the regulatory environment that has brought the focus and rigor to the quality control of the quantitative determination of drug concentration in biological samples. In this article, the author examines the regulatory findings discovered during the course of several years of auditing bioanalytical work. The outcomes of these findings underscore the importance of quality method validation to ensure the reliability of the data generated. The failure to ensure the reliability of these data can lead to potential risks in the health management of millions of people in the USA.     

Validation of bioanalytical chromatographic methods

A strategy is discussed for the validation of chromatographic methods that are developed to quantify drugs in biological matrices. Both the validation terminology and the hypothesis testing are briefly reviewed. The emphasis is on the design of the experiments required to allow a reliable conclusion about acceptance or rejection of the bioanalytical method. In particular, it is explained how to evaluate the calibration line, devise experiments to estimate precision and bias and how to determine the stability of the analyte between the time of the sample collection and the analysis of the processed sample.     

Guideline on bioanalytical method validation

在创新药物研发过程中,生物基质（如血清、血浆、血液、尿液、唾液）中的药物浓度测定是一个重要的方面。其数据可用于支持新活性物质的应用和仿制药及已授权药品的变更申请。动物的毒代动力学研究和临床试验,包括生物等效性研究的结果为原料药或产品的安全性和有效性提供关键性的数据支持。因此,应用经过充分验证并记录到一个满意标准的生物分析方法以得到可靠的结果,这是非常重要的。2012年2月1日,欧洲药品管理局（EMA）开始实施最新的《生物样品分析方法验证指南》（Guideline on bioanalytical method validation）,本指南适用于动物的毒代动力学研究和所有阶段的临床试验中获得的生物样品中的药物浓度的生物分析方法的验证。本文摘录其方法学验证部分,抛砖引玉,供相关研究人员参考。     

Tissue sample preparation in bioanalytical assays

Analytical quantitation of compounds in tissue has become a more prevalent addition to biological sample analysis in recent times. This increase will most certainly continue to bring the question of proper analytical method validation to the forefront of discussion. Thoughtful design of sample homogenization, analyte fortification and extraction can ensure a successful analysis. This review presents current trends in tissue sample preparation by harvesting, homogenization techniques, as well as concerns for calibrator and QC preparation. Strategies for consideration and resolution of common pitfalls in method development, for example stability issues and control biomatrices in endogenous analysis, are also presented.     

Method validation in the bioanalytical laboratory

Bioanalytical methods, based on a variety of physico-chemical and biological techniques such as chromatography, immunoassay and mass spectrometry, must be validated prior to and during use to engender confidence in the results generated. The fundamental criteria for assessing the reliability and overall performance of a bioanalytical method are: the evaluation of drug and analyte stability, selectivity, limits of quantification and detection, accuracy, precision, linearity and recovery. The extent to which a method is validated is dependent on its prospective use, the number of samples to be assayed and the use to which the data are put.

Specific analytical techniques may require additional validation such as antibody-binding characteristics, peak purity determination, evaluation of matrix effects or structural confirmation of the analyte. Ideally each assay should be cross-validated with a method utilizing a highly specific detector such as a mass spectrometer. Once in use, the performance of the method should be monitored using quality control standards. If a method is set up in another laboratory, the performance of the assay should be monitored with quality control standards sent from the originating laboratory.     

A training program in bioanalytical toxicology.

Students of diversified backgrounds are taught methods used in bioanalytical toxicology such as TLC, GLC, RIA, EMIT, UV, and spectrofluorometry. Major emphasis is placed on the detection of abused drugs in biologic specimens. It was found that the students with more advanced formal education have learned the lecture theory and instrumentation quicker and in greater detail. However, as far as the ability to work rapidly and accurately, many of the trainees who have had less formal education have shown better ability. Perhaps it could be said that the theory is a science, whereas the work is an art. This art through practice can be better developed by some people regardless of education. On completion of this training, they will be able to help fill the great need for toxicologic technicians.