Address the global regulatory requirements for the detection and quantification of N-nitrosamine as well as other mutagenic impurities in APIs and final drug products.

Mutagenic impurities pose a significant risk, even in trace amounts, as they can interact with DNA, potentially causing a carcinogenic response. Regulatory pressure to detect and quantify mutagenic impurities is increasing. Recently, regulatory agencies like the U.S. Food and Drug Administration and European Medicines Agency detected N-nitrosamine impurities (NDMA, NDEA, NMBA, etc.) in several blood pressure medicines (sartans) as well as in heartburn and stomach ulcers medicines (ranitidine). These findings not only led to drug product recalls and regulatory actions but also the development of specific guidelines for evaluating these mutagenic impurities with limits of detection ranging from ppm to ppb, well below those for other impurities as mentioned in ICH Q3A.

Agilent offers gas and liquid chromatography coupled with high- sensitivity triple quadrupole mass spectrometry and high-resolution quadrupole time-of-flight mass spectrometry for identification and quantitation of nitrosamines in active pharmaceutical ingredients (APIs) and drug products.

Featured Application Notes

Find application notes describing LC/MS and GC/MS methods for the detection and quantification of nitrosamine impurities.

• Analysis of Five Nitrosamine Impurities in Drug Products and Drug Substances Using Agilent GC/MS/MS Instrumentation
• Combined Analysis of N-Nitrosodimethylamine (NDMA) and N-Nitrosodiethylamine (NDEA) Using the Agilent 7697A Headspace Sampler, 8890 GC System, and 5977 GC/MSD (PDF)
• Determination of Nitrosamine Impurities Using the Ultivo Triple Quadrupole LC/MS (PDF)
• Determination of N-Nitrosodimethylamine (NDMA) Impurity in Ranitidine Using the Agilent 6470A Triple Quadrupole LC/MS (PDF)
• Determination of a Genotoxic NDMA Impurity Using the High-Resolution Agilent 6546 LC/Q-TOF in Ranitidine Drug Substance and Drug Products (PDF)
• Determination of Nitrosamine Impurities Using the High-Resolution Agilent 6546 LC/Q-TOF (PDF)
• How to Catch a Potential Mutagenic Impurity (PDF)

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