Packing materials for enantioselective preparative chromatography

This paper considers the application of chiral stationary phases to preparative liquid chromatography. The various types of CSPs are briefly reviewed in terms of their loading capacity, structure and general areas of application. Enantioselective preparative separations display certain aspects not necessarily encountered in more conventional achiral applications. These specifically involve the solubility of the target molecules in the mobile phases conventionally used in enantioselective chromatography. Strategies for the development of separations using mobile phases more suited to the requirements of preparative chromatography are outlined, with special reference to the use of carbohydrate-based CSPs. Since the selectivity is the most important, parameter in determining the usefulness of a particular set of separation conditions for preparative application, attention is also give to the optimisation of mobile, phase selectivity by variation of the nature of the solvent and also of the acidic or basic additives which may be used in the case of the separation of ionogenic solutes under "normal phase" conditions. In the scale-up of preparative separations to production scale, which is becoming of increasing importance of chiral pharmaceutical products and intermediates, an often misunderstood parameter is that of the influence of particle diameter, especially in the case of a SMB chromatography. The influence of particle size on the economics of large scale purifications is discussed and it is shown that, in contrast to the case of achiral separations where there is an economically optimum particle size, the particle diameter used for preparative enantioselective separations, even SMB, should be the smallest possible consistent with good column performance.