Analytical R&D and Quality Control

HPLC and GC method development for challenging separations including chiral separations

Rationale for HPLC Method Development for the API Release

1. Harmonize the testing of starting materials, intermediates and API into one method, if possible.
2. Use the API method for in-process-control. Alternatively, use a shorter method, preferably with the same column and mobile phase combination / compositions to provide consistency, in order to maximize the efficient use of each instrument.
3. Apply a retrospective approach to method development. Start development first on the API method and then add the starting materials and intermediates to the method to check the overall method suitability.
4. Evaluate method specificity during process development to ensure that adequate specificity is provided for the current process.
5. Conduct forced degradation to evaluate the method specificity for the degradants.

Forced Degradation and Understanding of Degradation Pathway

The intent is to provide an experimental design that will generate appropriate amounts of degradants that are likely to occur during the stability study. The cross functional scientific team charged with this body of work consists of organic and analytical chemists, which supports a more comprehensive understanding of the degradation pathway.

Chiral Separations

• A wide selection of chiral columns for use with the Column Spiderling provides for quick screening for chiral separations.
• Experienced analytical chemists with training in organic chemistry provide for efficient and rational method development / optimization.
• Extensive experience with compounds that contain 2 or more chiral centers.

Method Development with HPLC-CAD

Extensive experience with method development / optimization / troubleshooting using Charged Aerosol Detection (CAD).

Genotoxic Impurities

LC-MS and GC-MS is available for quantitative analysis of genotoxic impurities (GTIs) at ppm levels. These techniques provide a robust and cost efficient strategy for monitoring GTIs of interest.

Method Verification / Validation

Method verification / validation protocols are prepared following a phase-appropriate strategy and are submitted for review by the client. Methods can be developed in-house, adopted from the client, or transferred to a client’s designated laboratory.

Reference Standard Certification

Complete reference standard certification can be conducted in-house. The chemical characterization typically includes structure elucidation by complete multi-nuclear and multi-dimensional NMR peak assignment), HR-MS, FTIR, and UV. The physical characterization includes XRPD, DSC, DVS and PSD.