ABSTRACT
It is well known that enantiomers can exhibit completely different physiological and biological activities, as well as pharmacodynamic and pharmacokinetic characteristics. Therefore, it is very critical to control the enantiomeric purity of drug substances. The U.S. Food and Drug Administration has been issuing guidelines for drug development requiring the analysis and control of the enantiomeric purity of drug substances [1]. During the development of chiral API, analytical methods are needed for the determination of chiral purity. Owing to the increase of the number of compounds in the earlier phase of the drug development, speed and efficiency in method development have become increasingly important. Supercritical fluid chromatography has been used for chiral separations and has gained popularity over the years, especially for high-throughput chiral purifications and fast column screening for method development [2-8]. Advantages gained from SFC are the result of the properties of supercritical carbon dioxide such as low density and viscosity, high diffusivity, low cost, and easier solvent removal. Faster analysis, better separation efficiency, less solvent consumption, and longer column life are the typical characteristics of chiral separation with SFC. These characteristics make SFC a superior choice when it comes to chiral analysis. 8.2.2 Chiral Purity Analysis by SFC in Process Analytical
Chiral purity analysis has been conducted using SFC in process analytical chemistry for all types of materials, from raw materials, starting materials, intermediates to in-process tests for the manufacture of intermediates and APIs. The analysis of tartaric acid by SFC served as one of the example of raw material analysis [9]. The chiral purity analysis is needed as the incoming material test. The initial literature search returned little information on the chiral separation on tartaric acid. Method
development was initiated using SFC by employing a Chiralpak AD-H column as the chiral stationary phase (CSP). As shown in Fig. 8.1, baseline resolution is achieved in less than 3 min with 20% modifier. The modifier content is ethanol containing 0.1% (v/v) trifluoroacetic acid (TFA) as additive.
