NDSRI Risk Assessment and Trace-Level Analysis of N-Nitrosamines

Monday, October 21, 2024

1:30 PM – 2:30 PM MT

Location:360 Stage #3, Exhibit Hall

Sponsored By

Manufacturing and Analytical Characterization

Partner Presentation-Manufacturing & Bioprocessing

Partner Presentation Speaker(s)

Moritz Perscheid, PhD, MBA (he/him/his)

Senior Global Segment Manager
LGC
Luckenwalde, Brandenburg, Germany

Handouts

Description: N-nitrosamines, potent carcinogens regulated by the FDA and EMA, pose significant risks even in trace amounts. Sertraline, a common antidepressant, is particularly susceptible to forming the carcinogenic N-nitroso-sertraline due to its secondary amine group.
The acceptable intake level is defined by the CPCA approach, supported by in-vivo studies, and root causes are discussed on the backdrop of recent FDA guidance to the industry. Typically used excipients are discussed with respect to nitrite levels and formation of NDSRI in the drug product.
To address the analytical challenges of detecting NDSRIs, particularly N-nitroso-sertraline, LGC in collaboration with Waters Corporation, developed a robust UPLC/MS/MS method utilizing Ultra-Performance Liquid Chromatography with electrospray ionization (ESI) and the Xevo™ TQ-S micro Tandem Quadrupole Mass Spectrometer. The method, optimized with the Nitrosamines Impurity Quanpedia database, ensures precise quantification with excellent linearity (0.25-100 ppb, R² >0.99), high recovery (85-93%), and precision within ±20% of the true value.

Learning Objectives:

Demonstrate the complete workflow of Sertraline Hydrochloride drug substance and drug product NDSRI analysis using LGC standards and Xevo TQ-S micro tandem quadrupole mass spec from Waters Corporation.
Examine trace-level detection capabilities for N-nitroso Sertraline, aligned with Health Canada's revised acceptable daily intake limit, reduced from 1500 ng/day to 100 ng/day.
Develop and refine robust methods for the accurate quantification of N-nitroso Sertraline.