Fundamentals of Preparative and Nonlinear Chromatography

Georges Guiochon, Attila Felinger, Dean G. G. Shirazi

• Publisher: Academic Press
• Year: 2006
• Print ISBN: 9780123705372
• eBook ISBN: 9780080457222
• Edition: 2
• Topic: Physical Sciences
• Subtopic: Analytic Chemistry

Fundamentals of Preparative and Nonlinear Chromatography, Second Editionis devoted to the fundamentals of a new process of purification or extraction of chemicals or proteins widely used in the pharmaceutical industry and in preparative chromatography. This process permits the preparation of extremely pure compounds satisfying the requests of the US Food and Drug Administration. The book describes the fundamentals of thermodynamics, mass transfer kinetics, and flow through porous media that are relevant to chromatography. It presents the models used in chromatography and their solutions, discusses the applications made, describes the different processes used, their numerous applications, and the methods of optimization of the experimental conditions of this process.

Chapter 1

Introduction, Definitions, Goal

Contents

1.1 History of Chromatography

1.1.1 Discovery by Tswett and Early Works

1.1.2 The Rebirth of Chromatography

1.1.3 The Manhattan Project and the Purification of Rare Earth Elements

1.1.4 The API Project and the Extraction of Purified Hydrocarbons from Crude Oils

1.1.5 Preparative Chromatography as a Separation Process

1.2 Definitions

1.2.1 Linear and Nonlinear Chromatography

1.2.2 Ideal and Nonideal Chromatography

1.2.3 Separation, Extraction, and Purification

1.2.4 The Various Scales of Preparative Chromatography

1.3 Goal of the Book

References

Introduction

Chromatography was born as a preparative technique [1] at the turn of the last century. This was a time when there were no physical methods of analysis, when the acquisition of physico-chemical data was slow and limited to a few parameters of low specificity (e.g., melting points, densities, refraction indices). Analytical methods were essentially based on chemical reactions, they were slow, and had a poor sensitivity. Originally designed to extract purified plant pigments from complex mixtures of vegetal origin, chromatography had to be used with sequential fraction collection, followed by the off-line analysis of these collected fractions. In the early 1950s, the development of sensors, transforming the variations of physical or physicochemical properties into a current or a voltage and now known as detectors, and that of recorders of the electric signals provided by these sensors transformed science. With the invention of these devices, modern instrumentation changed profoundly the way in which chemists use chromatography.

In the early days of chromatography, the lack of sensors and the need to perform chemical reactions on the isolated fractions to identify and quantify their components imposed off-line detection. Then, the relative lack of sensitivity of most of the chemical methods of detection available at the time dictated the use of large-diameter columns, the injection of large samples, and the handling of only concentrated sample solutions. All these reasons combined made the chromatographic technique nonlinear, resulting in strongly unsymmetrical individual band profiles. Moreover, under such conditions, the retention times and the band shapes depend not only on the amount of each component in the sample, but also on the composition of that sample.

It was only in the mid-1950s that the development of gas chromatography [2] and the rapid progress made in the field of instrumentation permitted a considerable reduction in the column loading and made possible the operation of columns under linear conditions. Progressively, (1) the advancement of on-line detection, of on-line recording of the eluent composition, and later of the automatic integration of the peak area; (2) the development of new, extremely sensitive detectors; and (3) the progressive extension of on-line detection with very sensitive detectors to all the modes of chromatography led to the close association in the minds of analytical chemists between analytical chromatography and operation under linear conditions. Finally, a stage was reached where column overloading was considered to be an error, if not a sin, and was avoided at all costs. From there, preparative chromatography had to be rediscovered: a mental process that requires the painful revisitation of our knowledge and the reassessment of many rules and principles.

For the last forty years, there has always been interest in the use of chromatography for the purification of valuable compounds. Several attempts at commercializing and popularizing preparative gas chromatography were made in the 1960s and 1970s. They met with little success [3–5]. The main reasons for these failures were economic. Few compounds are both valuable enough to justify the extraction/purification costs of this process and volatile enough to be purified at an affordable price by preparative gas chromatography.

The rapid development of the fine chemical, pharmaceutical, and biotechnology industries during the last twenty years has combined with the pressure of the regulatory agencies. Their effort has led to the production of many high-purity chemicals to be used as pharmaceuticals or pharmaceutical intermediates, to the identification of the metabolites of these compounds, and to the completion of systematic studies of the toxicological properties of potential drugs and of their metabolites prior to their approval. This endeavor has generated the need to separate, extract, and purify many chemicals in the laboratory or at the industrial scale. Moreover, traditional techniques such as distillation, counter-current or centrifugal extraction, and crystallization used by the petroleum and the commodity chemical industries do not meet the needs of the pharmaceutical industry. No industrial separation technique is more versatile than chromatography, nor better suited for the rapid production of milligram to ton quantities of highly pure products. None has a comparable separation power. In recent years, preparative chromatography has been adopted as an industrial process in the pharmaceutical industry. Units with a production capacity ranging from a few pounds to more than a thousand tons per year have been built.

In the meantime, the chemical industry has developed numerous processes based on the use of adsorption. The complexity of these processes has been increasing constantly. Some of the recent ones are based on the use of chromatographic principles. This is the case for separation processes based on the simulated moving bed concept [6–8]. Initially developed for the extraction of a few specific compounds from complex mixtures, such as para-xylene from reforming streams or fructose from corn syrup, these processes are competing with the simpler chromatographic processes evolved from direct scaling-up of the laboratory procedures. Currently, equipments for overloaded elution may achieve production rates of up to 500–1000 ton/year or above and can handle most complex mixtures. Simulated moving bed units have been built with production rates between a few pound/year to more than a million ton/year. These equipments are unsurpassed for the separation of binary mixtures (e.g., enantiomers). A variety of recycling processes involving elution can fill in the gap.

1.1 History of Chromatography

Tswett (1872–1919) was ahead of his time. A long induction period followed the tragic interruption of his work during the Russian civil war and his untimely death. Not until the early 1930s did the importance of chromatography became recognized among chemists involved in the study of natural products [9] and biochemists who continued to play a critical role at several stages of development (e.g., in the discoveries of paper chromatography [10], gas chromatography [2], size exclusion chromatography [11], and affinity chromatography [12], among others).

With the progress made in the development of sensitive detection methods, analytical and preparative chromatography parted in the late 1940s. The first major preparative chromatography projects were the purification of rare earth elements by the group of Spedding [13] for the Manhattan project, and the isolation of pure hydrocarbons from crude oil by Mair et al. for the API project [14]. Later followed the development of the simulated moving bed technology by Broughton for UOP [6]. Finally, in the 1980s, the pharmaceutical industry began to show interest in high-performance preparative chromatography and this interest has been increasing steadily over the last twenty years [15]. Chromatography is now acknowledged as an industrial unit operation for the extraction and the purification of fine chemicals, particularly those used as pharmaceutical intermediates.

1.1.1 Discovery by Tswett and Early Works

The story of the discovery of chromatography is classical [16, 17]. A most lucid analysis of Tswett’s work from the point of view of the preparative applications of chromatography, has been written by Verzele and Dewaele [18]. The Russian botanist Tswett discovered around 1902 that plant pigments could be separated by eluting a sample of plant extract with a proper solvent on a column packed with a suitable adsorbent [1]. Did he name the technique chromatography because it separates pigment mixtures into a rainbow of...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Preface
• Acknowledgments
• Chapter 1: Introduction, Definitions, Goal
• Chapter 2: The Mass Balance Equation of Chromatography and Its General Properties
• Chapter 3: Single-Component Equilibrium Isotherms
• Chapter 4: Competitive Equilibrium Isotherms
• Chapter 5: Transfer Phenomena in Chromatography
• Chapter 6: Linear Chromatography
• Chapter 7: Band Profiles of Single-Components with the Ideal Model
• Chapter 8: Band Profiles of Two Components with the Ideal Model
• Chapter 9: Band Profiles in Displacement Chromatography with the Ideal Model
• Chapter 10: Single-Component Profiles with the Equilibrium Dispersive Model
• Chapter 11: Two-Component Band Profiles with the Equilibrium–Dispersive Model
• Chapter 12: Frontal Analysis, Displacement and the Equilibrium–Dispersive Model
• Chapter 13: System Peaks with the Equilibrium–Dispersive Model
• Chapter 14: Kinetic Models and Single-Component Problems
• Chapter 15: Gradient Elution Chromatography under Nonlinear Conditions
• Chapter 16: Kinetic Models and Multicomponent Problems
• Chapter 17: Simulated Moving Bed Chromatography
• Chapter 18: Optimization of the Experimental Conditions in Preparative Chromatography
• Glossary of Symbols
• Glossary of Terms
• Index