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

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.

Cost-effective, green HPLC determination of losartan, valsartan and their nitrosodiethylamine impurity: application to pharmaceutical dosage forms

“…Although LOS and VLS were studied, in a dense way, alone or in combinations with other drugs using different analytical techniques [2,[12][13][14][15][16][17], few literatures were reported for their determination with nitrosamine impurities. Determination of VLS and LOS with NDEA either alone or together was reported mainly using GC or LC with MS/MS detectors [18][19][20][21][22][23][24][25][26][27]. Despite the advantages of selectivity and sensitivity of mass detectors, they have two main defects.…”