Ever since sartan-containing medicines had to be recalled from the market in the summer and autumn of 2018 due to nitrosamine contamination, Swissmedic's own lab, OMCL (Official Medicines Control Laboratory), has been testing sartans with a critical chemical structure for nitrosamines. The test method which the lab developed especially for this purpose has now been refined in order to further improve the sensitivity of testing for nitrosamine contamination.
The test method (first published in mid-December 2018) that has now been upgraded is used to determine whether the amounts of N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) contained in valsartan and related sartans are above or below the safety limit The method is based on the use of gas chromatography–mass spectrometry (GC-MS).
The updated test method (31_PV_169) for measuring the permissible amounts of NDMA and NDEA is more robust and sensitive than the original one. The limits of detection (LoD) and limits of quantitation (LoQ) in the different active substances are as follows:
|Pharmaceutical active substance||NDMA||NDEA|
|LoD [ppb*]||LoQ [ppb*]||LoD [ppb*]||LoQ [ppb*]|
This concentration states how many units by weight or volume of one substance are contained in billions of units in another substance (1 ppb = 1 µg/kg).
Since the beginning of 2018, a number of Official Medicines Control Laboratories (OMCLs) in the General European OMCL Network (GEON) have been taking part in investigations contributing to the complex analytical methods used for detecting nitrosamines in sartans. The Network regularly publishes the test methods used in the various analytical procedures.
Safety limit test method for NDEA/NDMA in sartans based on GC-MS (31_PV_169) (PDF, 202 kB, 23.07.2019)(the document is currently only available in German)