Current Status and Trends of LC/MS(n) Application in Trace Level Impurity
Identification in Pharmaceuticals
 Tuesday,  March 4, 2008
8:30 a.m., Room 265 

Organizer:

Arindam Roy, Covidien

Speakers:

8:35      Impurity Identification:  More Information and Fast Decision-Making with Increased Sampling and Control  MIKE S LEE, Milestone Development Services, Kenneth Lewis, Steven M Fischer

9:10    LCMS(n) Analysis of Impurities in Drug Products and Drug Substances: Current Status, Strategies and Case Studies Using Unit Resolution and High Resolution MS  ARINDAM ROY, Covidien

9:45      Evaluation of the Importance of Accurate Mass, Mass Resolution and Dynamic Range for Impurity Profiling Applications Using Multistage Mass Spectrometry  DAVID A WEIL, Agilent Technologies, Patrick Perkins, Michael Zumwalt

10:20    Reaction Monitoring and Impurity Analysis for Drug Substance Synthesis  HEEWON LEE, Boehringer Ingelheim

10:55    LC/MS, LC/MS/MS and H/D Exchange Methodologies for Structural Characterization of Impurities and Contaminants in Pharmaceuticals  BIRENDRA N PRAMANIK, Schering-Plough

Overview:

Liquid Chromatography hyphenated with Tandem Mass spectrometry (HPLC/MSn) is used routinely to identify impurities/degradants in the drug development process. The importance of this technology is ever higher now with the new regulations for determination and control of genotoxic impurities due to the lower level (1 to 20 ppm) release criteria. Routine impurity analysis in pharmaceuticals requires identification at levels of 0.1 % (sometimes at levels of 0.05%) depending on the dose. LC/MS(n) has been a very useful tool to find out the molecular masses of the impurities on the fly before proposing a possible impurity structure, which corresponds to the particular mass during the early/later phase of drug development. In the earlier phase of the drug development, the process related impurities don’t have reference standards. Before we attempt to synthesize any particular impurity proposed in the process it is essential to get as much structural information as possible about the impurity of interest. LC-Tandem Mass Spectrometry (HPLC/MSn) can be used to elucidate and propose structures of the impurities/degradants generated in the process.
 
This symposium will focus on the current state and trends of LC/MS(n) applications in the small molecule drug development process, from a qualitative perspective relevant to the modern pharmaceutical industry. The latest advances of LC/MS(n) accurate mass measurement, dynamic range, H/D exchange, increased throughput and structure elucidation will be discussed from the application perspective along with its role in reaction monitoring during the process development.