Scale-Up of Analytical Methods

This optimization approach has the advantage of being fast and simple, but it often overlooks specific effects that happen at larger loads. These effects concern the displacement of one product by another and have been described by Guiochon and co-workers [25-28] and Cox and co-workers [29-31]. The interplay of adsorption isotherm, peak form, and capacity factor k during overloading of a column is depicted in Rgure 21-3 [32]. 

Sometimes, during the course of determining the capacity of the stationary phase and the adsorption isotherms, it turns out that significant preparative amounts of reference material can easily be obtained even with analytical 

TABLE 21-2. Calculated Production Scenarios for a Preparative Enantioseparation of a Morphanthridine Analogue on Chiralpak-AD 

Amount of CSP Analytical Column Pilot Plant Column Production Column 

3 Purity of Solvents, Stability of Products and Work-up. The quality aspect of the solvents used as mobile phases should not be forgotten, since the evaporation residue from the mobile phase can be significant. Assuming an average product concentration of 1-2 g/L mobile phase, it becomes obvious that an evaporation residue of lOmg/L solvent leads to Ig of evaporation 

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A drawback of displacement chromatography is the fact that optimum conditions cannot be found by scaling-up of analytical methods." However, after a successful but more or less time-consuming optimization of the displacement system, no other method allows this high throughput per unit time with this low consumption of the mobile phase. 

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