Combined N-Nitrosodimethylamine (NDMA) and N-Nitrosodiethylamine (NDEA) Impurity Assay by GC/MS-Headspace in valsartan

Valsartan products are used to treat high blood pressure and congestive heart failure. On July 13, 2018, FDA announced a recall of Valsartan tablets because of the potential for certain products to contain an impurity, N-Nitrosodimethylamine (NDMA). A second impurity was subsequently reported, N-Nitrosodiethylamine (NDEA). NDMA and NDEA are classified as probable human carcinogens and were believed to have been introduced into the finished products because of the manufacturing processes used to make the drug substance. OTR has developed a gas chromatography-mass spectrometry (GC/MS) headspace method to detect the presence of NDMA and NDEA in valsartan drug substance.

The combined method has been validated to simultaneously quantify NDMA and NDEA.

Impurity

N-Nitrosodimethylamine (NDMA)  LOD (ppm) - 0.005 LOQ (ppm)-0.10

N-Nitrosodiethylamine (NDEA) LOD(ppm)-0.02 LOQ(ppm) - 0.05

N-Nitrosodiethylamine (NDEA) -Structure (above)