Analytical Strategies for Improved Sensitivity, Selectivity, and Quantitation of Genotoxic Impurities

Solving Problems That Matter: Nitrosamine Analysis

Expert Insight 3-Part Webinar Series: Upskilling Your Analytical Strategies for Nitrosamine Detection and Control to Proactively Address Safety in Pharmaceutical Product Development.

Unacceptable levels of N-nitrosamine impurities, which may increase the risk of cancer, have been found in some medications resulting in drug recalls, warning letters, and therapeutic shortages. To ensure that the residual level of nitrosamines in your drug products related to your drug development and manufacturing processes is within safe amounts, highly sensitive and specific analytical methods need to be used for the detection, characterization, and quantification of such impurities. Learn how your colleagues have upskilled their lab capabilities and technologies to elucidate the nature of unknown materials in complex drug substances, using a variety of analytical techniques.

In this timely virtual webinar series, pharmaceutical scientific experts discuss key analytical strategies on how to improve methods for nitrosamine impurity detection and characterization, and how sharing this expertise can help your pharmaceutical scientists support your product quality, safety, and efficacy

PART 1 | Analytical Strategies for Improved Sensitivity, Selectivity, and Quantitation of Genotoxic Impurities

Genotoxic impurities (GTIs) are of major concern to the pharmaceutical industries and regulatory agencies around the world as they could potentially induce genetic mutation/damage. Limiting and controlling their levels of Drug Substance and Drug Product is critical in ensuring patient safety and drug product quality.

Typically, the maximum acceptable levels of these impurities are usually in low parts per million based on the maximum daily dose and duration of exposure. Compared to classical impurities, analysis GTIs/PGIs are extremely challenging if not impossible as the detection limits are typically several orders of magnitude lower requiring techniques of high-sensitive and selectivity, usually chromatographic techniques with mass spectrometric detection to enable an ultra-trace analysis of these impurities. These limits are further lower for the nitrosamines posing challenges to modern-day analytical instrumentation. However, an area often overlooked and underexploited in GTI analysis is the capabilities of modern-day analytical instrumentations and column technologies providing desired sensitivity and selectivity for these compound classes.

The presentation will emphasize strategies to improve the sensitivity and selectivity of GTI analysis including the use of in-line mixing modulation, a simple novel approach to push detection limits lower; a decision tree for systematic analysis of GTIs taking into consideration their volatility, liability, and detection limits. Additionally, the strategy for the filing of Genentech's first small molecule Erivedge will be presented.

Presenter: C.J. Venkatramani (Distinguished Scientist, Genentech, USA)

C.J. is a distinguished scientist at Genentech, USA, and has more than 15 years of experience in the pharmaceutical Industry. He was a key member of the Genentech technical team instrumental in the successful launch of Genetech’s first small molecule, Erivedge, leading from development to commercialization. Erivedge is currently approved in several countries around the world for the treatment of advanced basal cell carcinoma (BCC). His area of interest includes 2D-LC, 2D-LC-SFC, and ultra-trace analysis of genotoxic impurities. Over the years, he has successfully used multidimensional chromatography to address challenging problems encountered in the pharmaceutical industry.