Impurities/Degradation Products in Drug Substances: Innovative Approaches to Control the Process

Session 710, Room 267, 1:30 p.m.

This organized contributed session was arranged by Andy Miles and Paul Wrezel of Regis Technologies, Inc. Miles will preside over the session, which will start at 1:30 p.m. this afternoon.

Wrezel will give the first talk titled “Selected Case Studies Involving Method Development for Trace-Level Impurities.”   According to the abstract, this presentation will review case studies involving method development of trace-level impurities in drug substances as well as starting materials and intermediates. Chemical derivatization, high performance liquid chromatography (HPLC), and mass spectrometry (MS) techniques, which are used in developing methods for the control and monitoring of impurities and degradation products, will be discussed.

The second talk in this session will be given by Tony Yan of Pfizer on “Drug Impurity Isolation for Structure Elucidation.” According to the abstract, Yan will provide a general overview for the impurity isolation strategy including various purification technologies, column chromatography, analytical method development for optimizing the resolution, and the discussion on impurity structure work flow.

Todd Zelesky, also of Pfizer, will present next. His talk is titled “Integrating the Chemistry of Drug Degradation into the Structure Elucidation Workflow: A Focus on Sample Enrichment.” According to the abstract, case studies will be presented to highlight sample enrichment and isolation process that ultimately support MS and nuclear magnetic resonance (NMR) structure elucidation of targeted low level drug product degradants.

Igor Likhotvorik of Regis Technologies, Inc. will give the fourth talk in this session. The talk is titled “Structure Elucidation of Impurities in Drug Substances by 2D NMR” and will discuss practical strategies and tactics for establishing structural connectivity using two-dimensional (2D) NMR. Case studies of the structure elucidation of impurities in drug substances will also be presented.

After a brief 10-min recess, LCGC columnist Michael Dong will give a talk titled “HPLC Method Development for New Drug Candidates with Multiple Chiral Centers.” Dong will describe the method development and quality control (QC) strategies used for complex multichiral drug molecules, which include:
• Adoption of a three-pronged HPLC method development template approach 
• Development of a single reversed-phase method using multisegment gradients for determination of overall purity and diastereomeric content
• Supercritical fluid chromatography (SFC) for rapid initial screening for chiral separations 
• 2D LC for peak purity determination and achiral/chiral combinational assays
 

Ray McClain of Merck will give the next talk titled “Isolation and Characterization of Impurities in Support of Drug Discovery and Development.” McClain will highlight modifications made to preparative instrumentation traditionally used in the high-throughput arena to maximize performance for these challenging samples. Characterization data generated for the isolated compounds will be presented to demonstrate the array of information that can be derived from the small sample size with state of the art instrumentation.

The final presentation in this session will be given by Matthew Przybyciel of ES Industries. Przybyciel’s talk is titled “Exploring the Separation Power of HILIC for the Analysis of Polar Impurities” and it will present a strategy for the HPLC analysis of polar compounds using hydrophilic-interaction chromatography (HILIC) conditions. In addition, the potential limitations of HILIC chromatography will be discussed including dynamic/linear range, retention time reproducibility, mobile phase composition, and potential sample matrix effects.