Separation Methods in Drug Synthesis and Purification [antikvár]

Editoras preface In the pharmaceutical industry our aim is to discover and develop drugs in a cost-effective way The new technologies such as combinatorial chemistry high throughput screening, and robotics have made it possible to synthesise millions of molecules for thousands of screens. We need efficient methods to check the quality and the quantity of the new molecular entities, and this is where separation science plays an important role. The process of selecting candidate molecules needs to be accelerated and the number of molecules failing in a later stage of the development process has to be reduced. Separation science can help in selecting molecules for further development, in greater productivity of compound progression, to shorten drug development cycles and to build in better quality at an early stage. For all of the above-mentioned purposes we need separation techniques that are readily available, easily implemented and reproducible with instrumentation that is well developed and supported by the manufacturer. The objective of this book is to provide a critical rather than a comprehensive review of the analytical separation methods and techniques used in the pharmaceutical industry. We shall concentrate on to the applied separation science and technologies used across the early stages of drug research, synthesis, and purification. We do not intend to cover the separation methods used in quality control, formulation, toxicology, and pharmacokinetic studies, although very similar techniques and methods can be used in these areas. The academic contributors will provide guidance to the various separation methods, their relative value and advantages and their pitfalls. They provide a source of established and potential methods based on the literature that can be consulted by the reader. The contributors from industrial backgrounds reveal the aspects of various methods from the industrial viewpoint and will focus on discussing useful technologies, such as automation, cost impact and organisational issues in conjunction with the separation methods. Therefore this book can be used as a reference to methods frequently used in pharmaceutical research and development. Some of these methods may be very new and may not have been published before but they have been tested in everyday work. Although many of the industrial contributors are my colleagues at GlaxoWellcome we do know that in other pharmaceutical companies similar approaches and technologies are used with very similar aims. The most widely discussed technique throughout this book is high performance liquid chromatography. The reason for this is that there are many advanced applications of this technique to a wide selection of problems bringing also the benefit of automated analysis. The theoretical background and practical solutions of the gradient method will be highlighted together with the hyphenated techniques (i.e. HPLC with mass spectrometry or NMR). The comparison of isocratic and gradient methods, which is crucial when we want to u.se information from one method or the other, will be discussed. To avoid the time taken for method development for