Method Development and Forced Degradation
Our Typical Method Development Projects
❖ Development of HPLC/UPLC assay and impurities methods supporting various stages of drug development programs
❖ Forced degradation studies and assessment of the degradation pathways of the NCE (including ID of the major degradation products)
❖ Development and qualification of LC/MS methods with SIM mode (or other methods as appropriate) for quantification of PGIs (potential genotoxic impurities) at the ppm levels
❖ Chiral HPLC method development and qualification
❖ Development of dissolution methods for various stages of drug development (including appropriate discriminating methods in support of NDA)
❖ GC methods supporting analysis of various volatile compounds and drug product residual solvents, following ICH guidelines
❖ Re-development, troubleshooting and fixing deficiencies of the existing methods. Conversion of long HPLC assay/impurities methods (sometimes with several actives) into shorter and more efficient UPLC methods
Forced Degradation and Understanding of the Degradation Pathway
Forced degradation is an integral part of impurity evaluation in method development, which is undertaken to facilitate development and to demonstrate the suitability of stability indicating methods. This is particularly important when little information is available about potential degradation products.
Forced degradation studies generally rely upon conditions that promote thermolytic, hydrolytic, oxidative, and photolytic degradation mechanisms. The goal of these studies is to generate a primary degradation profile that mimics or exceeds what would be observed in accelerated stability studies conducted under ICH conditions.
EZ Labs scientists design experiments to generate similar amounts of degradants to those occurring in stability studies. A team of analytical chemists can thus achieve a comprehensive understanding of the relevant degradation pathway.
Chiral Separations
The presence of stereocenters in intermediates and Active Pharmaceutical Ingredients (APIs) add an additional layer of required analytical understanding, monitoring and control. Each enantiomer or diastereomer may have great variations in efficacy and toxicity. In 1992 the Food & Drug Administration (FDA) issued a series of guidelines for the development of single enantiomers and racemates in pharmaceuticals.
We can rapidly screen a wide selection of chiral columns and then further optimize the resulting chiral HPLC method.
Our team of analytical chemists with extensive experience with poly-chiral compounds facilitates efficient and rational method development / optimization.
Method Development with HPLC-CAD
Charged Aerosol Detector (CAD) is a universal detector and (in conjunction with HPLC) can be used to measure all non-volatile (and some semi-volatile) compounds. This renders it extremely useful in the evaluation of purity and quantification of impurities for new drug candidates or intermediates lacking a significant UV chromophore.
EZ Labs successfully developed and qualified CAD based methods for a number of our clients and thus has a deep-rooted experience base in gaining invaluable knowledge with method development / optimization / troubleshooting with this mode of detection.