Methods for determination of NDMA and NDEA in sartans
The Official Medicines Control Laboratories (OMCLs) of the General European OMCL Network (GEON) are involved in investigations and actions to address the issues related to the detection of N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) in valsartan and related sartans. The Network has developed methods for the specific testing of nitrosamines in sartans on the basis of different analytical principles.
The Irish OMCL in the Public Analyst’s Laboratory in Galway (PALG), the French OMCL at the ANSM site in Montpellier, the German OMCL at the “Chemisches und Veterinär-Untersuchungsamt (CVUA) Karlsruhe”, the OMCL at Swissmedic and the Bavarian OMCL at the “Landesamt für Gesundheit und Lebensmittelsicherheit (LGL)” established different methods on behalf of the Network.
These methods are publicly available and can be accessed below:
- This LGL method is a GC-MS screening method for the determination of NDMA and NDEA in sartan drug substances (valsartan, irbesartan, losartan, candesartan, olmesartan).
- This LGL method is based on LC-MS/MS (similar to the CVUA Karlsruhe method) and suitable for the determination of NDMA and NDEA in irbesartan, valsartan, and losartan drug substances and products.
- This Swissmedic method (limit test) is based on GC-MS (Liquid-direct-injection) and allows determination of both NDMA and NDEA simultaneously in sartans. Please note that prior to use, the method must be appropriately validated. The German version is the official version. In order to access the official version please use the following link.
- NEW: This revised CVUA Karlsruhe method is based on UHPLC-APCI-MS/MS and allows determination of both NDMA and NDEA simultaneously in sartans; the method is now validated for valsartan, irbesartan, losartan and candesartan containing film-coated tablets with or without hydrochlorothiazide.
- This CVUA Karlsruhe method is based on UHPLC-APCI-MS/MS and applicable to the detection and quantitative determination of NDMA in valsartan drug products.
- This PALG method is based on Headspace GC-MS (single quad) and applicable to the determination of NDMA in drug substances and corresponding powdered tablets of the sartan group.
- This ANSM method is based on HPLC-UV and applicable to the determination of NDMA in API and corresponding powdered tablets of valsartan.
Please note that OMCLs of the General European Network are by their status and role only performing tests on behalf of competent authorities and for that reason are not in the position to accept contract work for private companies.
The U.S. FDA and Health Canada have also published methods for determination of NDMA and NDEA.