This analytical note highlights a robust and sensitive procedure for the quantification of six nitrosamine impurities NDMA, NDEA, NDIPA, NEIPA, NDPA and NDBA in common (commercial and analytical) solvents used during pharmaceuticals manufacturing at trace levels by GC-MS/MS. The procedure was validated according to USP General Chapters <1225> and <736>
- LOQ of 0.005 ppm for NDMA, NDEA, NEIPA, NDIPA,
NDPA in analytical-grade solvents with respect to 100
mg/mL sample concentration.
- LOQ of 0.013 ppm for NDBA in analytical-grade solvents
with respect to 100 mg/mL sample concentration.
- LOQ of and 0.1 ppm for commercial-grade solvents
(NDMA, NDEA, NEIPA, NDIPA, NDPA and NDBA) with
respect to 25 mg/mL sample concentration.
- Accuracy and precision ≤20%.
This application note was developed to provide an analytical resource for regulators
and industry to monitor nitrosamine impurities in drug products, drug substances or other matrices. It is intended to serve as a resource for informational purposes only and not as an USP-NF compendial documentary standard. This document was developed by USP staff without a public comment period and does not reflect USP or USP’s Expert Body opinions on future revisions to official text of the USP-NF. Parties relying on the information in this document bear independent responsibility for awareness of, and compliance with, any applicable federal, state, or local laws and requirements.