, was not initially developed for analytical purposes, but for the isolation of some specific pigments from plant extracts. In fact, all the early applications of chromatograph were exclusively for preparative purposes and it was not until gas chromatography (GC) was introduced by Martin and Synge (1) was the technique used for analytical purposes. Even after the introduction of GC, liquid chromatography (then called column chromatography) was still used largely for preparative work. Liquid column chromatography evolved from a preparative procedure into an analytical technique during the late nineteen sixties, largely provoked by the development of high performance liquid chromatography (HPLC), which, in turn,  was largely sparked off by the successful development of GC. Initially, column loads were increased for preparative purposes by increasing the dimensions of the column both in GC and in HPLC. However, this approach has distinct limitations. If the column radius is

the pharmaceutical industry for the isolation and purification of physiologically active substances. There are a number of unique problems associated with preparative gas chromatography. Firstly, it is difficult to recycle the mobile phase and thus large volume of gas are necessary. Secondly, the sample must be fully vaporized onto the column to ensure radial distribution of the sample across the column. Thirdly, the materials of interest are eluted largely in a very dilute form from the column and therefore must be extracted or condensed from the gas stream which is also difficult to achieve efficiently. Finally, the efficient packing of large GC columns is difficult. Nevertheless, preparative GC has been successfully used in a number of rather special applications; for example the isolation of significant quantities of the trace components of essential oils for organoleptic assessment. The layout of a preparative gas chromatograph is shown in figure38

and tailing on the column. This procedure may entail sample recovery from the residue contained in sample valve. Preparative Columns Preparative columns (GC or LC) are usually made of glass or stainless steel the latter being used for high pressure systems. Preparative columns must be designed to accommodate the inlet pressure necessary to obtain the required flow rate through the packed bed which is determined by the size of the particles selected for the packing. The larger the column diameter, the stronger must be the column and the thicker the walls. Large column operating at high pressures with relatively small particles can become extremely bulky and heavy. In addition, the construction of wide columns (3 in. O.D. and greater), irrespective of the packing, can be extremely expensive to both construct and to pack and it is essential to take cost into all design considerations. Columns having diameters greater than 0.5 in. need to have the frit supported on a

economic limit to the scale of preparative chromatography, there does not appear to be any practical constraint to column size. Performance data from columns of over a meter in diameter have been reported which has shown that they can be operated very successfully. Unfortunately there is very limited design and operational data available for such columns due to the highly proprietary nature of their use. Large diameter columns, however, must have an appropriate sample distribution system at the column inlet. This is to ensure that the sample is dispersed evenly over the whole cross section of the column so that  the full capacity of the column is utilized and as a secondary consideration significant column efficiency is not lost. Although the actual column may need to be custom made, solvent pumps, with high volume delivery at moderate pressures, are readily available. Most of the pipe fittings, valves, etc. can be obtained from manufacturers that supply equipment for general chemical

LC Columns If particle sizes in excess of 20 mm are used, then the column can often be dry packed, with appropriate tapping, or, even better, with longitudinal and radial sonic vibration. The variance per unit length obtainable from a preparative LC column should be less than 2 particle diameters (determined using analytical scale samples). It is worth remembering that (as already discussed) when designing preparative columns, it is better to obtain the necessary efficiency using a longer column packed with larger particles, than the converse. The long column will permit much larger charges and, if pertinent for the sample concerned, will also allow multiple sample development techniques. In addition, the larger particles will provide greater column permeability, and thus lower pressures can be used. Lower pressures will, in turn, allow lighter and less expensive materials to be used in the construction of the preparative system

are other problems that need addressing, once packed, the practical lifetime of a column is also uncertain. The changes in performance of a preparative HPLC column that occurs with time depends upon the stability of the packed bed. Frequently, the bed settles after operation for even a short time and the top of the column needs to be repacked. Sometimes channels are formed in the bed, in which case the entire column has to be repacked. The rate of settling again depends upon the diameter of the column. This bed instability arises because there is a significant change in wall support as the column diameter increases. In analytical columns the walls are relatively close to the center of the column and 'bridges' of packing particles can be formed across the bed, as shown in Figure 16. These bridges allow the longitudinal forces acting on the packing within the column to be dissipated to the walls. When a column is packed, it is never in its optimal configuration and there are always areas