Large-scale chromatographic

The design of a production chromatograph is a complex exercise because of the many process variables involved. Some of the published work on optimisation proceeds from the unsatisfactory notion that a large-scale chromatograph is little more than a scaled-up analytical one into which large samples are injected. Thus the sample size is commonly chosen as the largest which does not excessively degrade resolution. 

In this chapter the three main modes of large-scale chromatographic operation, and combined reaction and separation. Many useful but small-scale chromatographic methods have been omitted, as well as allied separation techniques which combine aspects of chromatographic principles or practice with aspects of adsorption, extraction, sedimentation or electrophoresis. Such is the pace of invention that novel processes related to chromatography are still being developed and described in the literature. 

In contrast to the isolation of small molecules, the isolation and purification of microbial proteins is tedious and often involves a number of expensive large-scale chromatographic operations. 

Piston flow signifies that some of the liquid passes through the reactor in plug flow. This liquid, unlike that involved in short-circuiting, has a certain residence time in the reactor. In certain operations, it is essential that the flow approach as close as possible some ideal situation, usually plug flow (e.g., in continuous, large-scale chromatographic separations). 

As observed with this HEWL-Cibacron Blue F3GA immobilized Frac-tosil 1000 system, and numerous other cases of polypeptide or protein interaction with HPLC sorbents, the maximum production rate tends to increase with the increase of the terminating effluent concentration. At fluid velocities lower than the optimum velocities, the effect of the terminating effluent concentration, however, becomes less important. The use of a flow rate at the maximum capacity of the pump (or to the pressure limit of the system as is sometimes practiced) will usually lead to an impaired production rate with HP-BAC, HP-BMC, and HP-HIC sorbents.307,422,423 This conclusion has been also supported by other experimental data on large-scale chromatographic purification of proteins with HP-IEX sorbents.368,406,421,424... 

Backflushing A method for cleaning filters involving reverse flow throngh the membrane (or Back occasionally nsed for cleaning large-scale chromatographic columns. See... 

Berg, 0. W. An All-Glass Coupled Column for Large-Scale Chromatographic Separations. Analytic. Chem. 37, 774 (1965). 

Optimize chromatographic separations on a small scale before committing resources to large-scale chromatographic purifications. 

The chapter on resolutions has a number of examples as illustrations showing that this methodology is still important to obtain chiral compounds. Although, ultimately, it may not be the most cost-effective method, it can provide material in a rapid manner, and can usually be scaled up. The introduction of large-scale chromatographic techniques, as well as the availability of a large number of enzymes that can be used to perform reactions on only one enantiomer, will ensure that this approach remains a useful tool in the future. 

Combinatorial synthesis has been applied to the development of new chual stationary phases (CSPs) for large-scale chromatographic separations, which are becoming increasingly important due to the complexity of both synthesized as well as natural products. 

Breece T N, Gilkerson E, Schmelzer C (2002a). Validation of large-scale chromatographic processes, Part 1 Case study of neuleze capture on macroprep high-S. BioPharm. 15 16-20. 

Resolution of hydroxy lie compounds by chromatography. The chiral isocyanate is useful for large scale chromatographic separation of diastereomeric carbamates. The elution order is correlated with the structure and the stereochemistry. 

A number of alternative LC distributions systems (distribution systems other than simple columns) have been developed for preparative work which need to be discussed. Some of these have found limited use but, nevertheless, have been shown to be very effective for large scale chromatographic purification for certain types of application. 

Phosphane obtained by one of the laboratory methods described in the previous sections is generally purified by low emperature fractional condensation in vacuum [1 to 5]. The compound passes through a trap held at -120°C [1, 4], -126 C [5], -131°C [3] and condenses completely at -196 C [1 to 5]. Purification of larger amounts is achieved by low-temperature rectification [6 to 9], distilling in a packed column filled with activated zeolite [10] (see also [11, 12]), or large-scale chromatographic separation [13]. Molecular sieves, in particular zeolites, were used to remove HgO [7, 14 to 17, 37, 38]. The removal of HgO by ZnO-based moldings is described in [18, 19]. 

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