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

다국어 초록 (Multilingual Abstract)

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 = 0.0120x − 0.0202 (4.0–1080 μg/kg, r = 1.000) for NDMA, and y = 0.0144x − 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.
Rapid NDMA and NDEA impurity Search in Medicines.