Drug substances chromatographic techniques

SMB is now accepted as a real production tool. For instance, the Belgium pharmaceutical company U.C.B. Pharma announced recently the use of SMB for performing multi-ton scale purification of an enantiopure drug substance. The concept of large-scale purification of enantiomers using chromatographic techniques has moved from a dream to a reality within the last few years. 

Modern spectroscopy plays an important role in pharmaceutical analysis. Historically, spectroscopic techniques such as infrared (IR), nuclear magnetic resonance (NMR), and mass spectrometry (MS) were used primarily for characterization of drug substances and structure elucidation of synthetic impurities and degradation products. Because of the limitation in specificity (spectral and chemical interference) and sensitivity, spectroscopy alone has assumed a much less important role than chromatographic techniques in quantitative analytical applications. However, spectroscopy offers the significant advantages of simple sample preparation and expeditious operation. 

S. Klick, Evaluation of different injection techniques in the gas chromatographic determination of thermolabile trace impurities in a drug substance. Journal of Chromatography A, 1995, 689(1), 69-16. 

Many recent biochemical applications of gas chromatographic techniques have been given in a review by Juvet and Dal Nogare (1968). The treatment of steroids was particularly prominent. Other substances mentioned were drugs, vitamins, amino acids, peptides, carbohydrates, strains of bacteria, and various types of milk. 

In order to characterize the chiral nature of a drug substance, and to then track its optical purity on stability, a method which can resolve the subtle chiral differences between the main chiral form, and its optical isomer is required. The most robust way to measure chiral purity is to separate the two enantiomers by means of a chiral chromatographic technique. Once the species are separated, they can easily be quantitated by UV detection. In order to achieve a separation of two enantiomers, they must interact in some way with a second enantiomeric species. There are two general method of how to accomplish this chromatographic separation. ... 

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