Development and comparison of methods for the nitrosamine analysis in different APIs by means of UPLC-MS/MS


Pérez Brizuela, Sara


In recent years, nitrosamines have been detected as impurities in various drugs, finished products or active pharmaceutical ingredients (APIs). Although the concentration levels were low, their presence has led to the withdrawal of the affected drugs and a thorough investigation of the causes of the formation of these impurities, since nitrosamines are known to be potent genotoxic carcinogens. This situation has generated the need to develop more sensitive and selective analytical methods for the simultaneous determination and quantification of various nitrosamines in different APIs and finished products.
Most of the published analytical methods for the determination of nitrosamines in drugs are limited to the determination of N-Nitrosodimethylamine (NDMA) and N. Currently, the European Pharmacopoeia (Ph. Have presented some limit and quantification tests for the analysis of nitrosamines that will soon be mandatory.
In this work the IQS method for the determination of nitrosamines by UPLC-APCI-MS / MS is expanded and one of the nitrosamines required to the different monographs is incorporated: N-Nitroso-N-methyl-4-aminobutyric acid. Thus, the method allows the simultaneous detection of 12 nitrosamines: N-Nitrosomethylamine, N-Nitrosoethylisopropylamine, N.Nitrosomethylethylamine, N-Nitrosodiethylamine, N-Nitrosodiisopropylamine, N.Nitrosodipropylamine, N-Nit-Nitrosodibutylamine acid, N-Nitrosopyrrolidine, N-nitrosopyrrolidine, N-nitrosopyrrolidine acid , 4-Nitrosomorpholine and N-Nitrosodiphenylamine.
In addition, an exhaustive study has been carried out on the effect on the retention of both nitrosamines and different APIS (Almotriptan, Venlafaxine, Omeprazole, Lansoprazole, Disulfiram, Cinitapride and Bilastine) by varying both the aqueous component of the mobile phase (acid, basic, neutral and buffer) as the stationary phase of the chromatographic column. In this way, knowledge of the retention form of the different analytes under study is achieved, thus speeding up the development of future methods for determining nitrosamines in any active principle.



Gómez Canela, Cristian
Gotor Navarra, Gemma


IQS SE - Master’s Degree in Analytical Chemistry