Pharmaceutical Regulatory Agencies have issued specific guidelines regarding the development of chiral drugs.
Today chiral drug approval process requires to monitor chirality at each stage of drug development.
According to the guidelines, it is recommended:
- The pharmacologic activity of each individual enantiomers should be investigated.
- Pharmacokinetic and pharmacodynamic profiles of the individual enantiomers should be characterized.
- For single enantiomer development, the other enantiomer should be considered as an impurity and the ratio of enantiomers should be controlled
Consequently for preclinical trials:
- Grams of enantiomerically pure of both enantiomers are needed
- Enantiomeric purities must be determined
Analytical and preparative HPLC-based chiral methods which are fast and cost-effective are today preferred over asymmetric synthesis for single-enantiomer development and optical rotatory tests for enantiomeric determinations