Determination of nitrosamines – DSI-pharm implements a LC-MS/MS screening method for drug substances and drug products
Since the Valsartan scandal in June 2018, there has been a growing interest in the risk assessment of potential traces of toxic nitrosamines in drug substances and products. The Official Medicines Control Laboratories (OMCLs) of the General European OMCL Network (GEON) were involved in investigations and actions to address the issues related to the detection of N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA) and other relevant nitrosamines. The EMA gives manufacturers six months to complete risk based testing, and three years for all further necessary tests and implementation of the corresponding changes in the manufacturing license.
Based on a CVUA Karlsruhe method, DSI-pharm recently implemented a generic LC-MS/MS method with limits of quantification (LOQ) between 1 ng/mL and 5 ng/mL for 6 different nitrosamines including NDMA and NDEA (current spectrum of nitrosamines contained see Table and Figure 1). Samples of drug substances and products are tested for nitrosamine traces after being diluted in a solvent using liquid chromatography. This is coupled with mass spectrometry using atmospheric pressure chemical ionization (UHPLC-APCI-MS/MS) in multiple reaction monitoring mode (MRM).
Table 1: Nitrosamines included in method
The generic LC-MS/MS method can be easily adapted to different drug substances and products if necessary. The method must then be validated under GMP for each product. The final LOQ´s will range between about 0,010 ppm and 0,050 ppm depending on the nitrosamines and the required sample dilution. Upon request, further nitrosamines of interest can be implemented into the method.
DSI-pharm is highly experienced in trace and residue testing in food and pharma products and can offer you attractive turnaround times – also for method development and validation.
Do you have further questions about the analysis of nitrosamines?
Please contact our expert Dr. Serap Acikgöz:
+49 441 361 326 54 49