At AZ-Biopharm we established, after the development and validation of a GC-MS and an even more sensitive UHPLC-MSMS method for the determination of N-nitroso-dimethylamine (NDMA) in drugs and in APIs, a screening method for 12 nitrosamines.
The method combines the detection of N-nitroso-dimethylamine (NDMA), N-nitroso-diethylamine (NDEA), N-nitroso-dipropylamine (NDPA), N-nitroso-dibutylamine (NDBA), N-nitroso-piperidine (NPIP), N-nitroso-pyrrolidine (NPYR), N-nitroso-morpholine (NMOR), N-nitroso-methyl-ethylamine (NMEA), N-nitroso-methyl-4-amio-butyric acid (NMBA), N-nitroso-methylaniline (NMPhA), N-nitroso-ethyl-isopropylamine (NEIPA) and N-nitroso-diisopropylamine (NDIPA) in a single run. The current limit of quantification (LOQ) of the initially validated UHPLC-MSMS method for NDMA is 0.576 ng / ml, which corresponds to 0.0144 ppm in the sample (= 30% of the specification level of the metformin 1000 mg tablet). The detection limit (LOD) of this method is 0.288 ng / mL in solution, which corresponds to 0.0072 ppm in the sample (= 15% of the specification level with a signal-to-noise ratio> 10). Taking into account the signal-to-noise ratio> 10, there is the potential for a LOQ of 10% of the specification level (metformin), which would be particularly attractive for a reduced analysis volume. Since NDMA has the lowest retention time with the lowest ionization efficiency compared to the other compounds, we are sure that the screening method will detect all other listed nitrosamines with sufficient sensitivity.