Determination of N‐Nitrosodimethylamine and N‐Nitrosodiethylamine in Sartans and Metformin Raw Materials and Finished Products by Headspace Gas Chromatography‐Tandem Mass Spectrometry

A simple and sensitive headspace (HS) and gas chromatography‐isotope dilution tandem mass spectrometric method was studied to determine N ‐nitrosodimethylamine (NDMA) and N ‐nitrosodiethylamine (NDEA) in sartans and metformin raw materials and their finished products. The HS parameters were optimized and selected. Samples in headspace vial were extracted at 150°C for 15 min and analyzed by injecting 1.0 mL of the headspace into the gas chromatography–mass spectrometry (GC–MS)/MS system. The mass spectrometer was operated using the electrospray ionization and detection was performed in a multiple reaction monitoring mode. Under the established condition, the lower limits of detection was 0.4 μg/kg for NDMA and 0.1 μg/kg for NDEA by using 0.1 g of sample. The precision was in the range of 0.4–3.5% for NDMA, and 0.4–3.3% for NDEA, and the accuracy was in the range of 95.0–105% for NDMA and 93.6–103% for NDEA, respectively. The linear equation of the calibration curve is y = 0.0120 x − 0.0202 (4.0–1080 μg/kg, r = 1.000) for NDMA, and y = 0.0144 x − 0.0042 (0.5–288 μg/kg, r = 1.000) for NDEA. The developed method can be applied to all six sartans and one metformin raw materials and their finished products.