Supercritical fluid extraction assisted by magnetic solid-phase extraction method using MWCNTs/FeO@coPANI-PTH as preconcentration and gas chromatography mass spectrometry analysis for determining nitrosamines in Valsartan and Losartan tablets.

As of 2018, the drugs "sartans" have received massive attention, as they have been found to contain non-virtual amounts of nitrosamines (NAs) such as N-nitrosodiethylamine (NDEA) and N-nitrosodimethylamine (NDMA). In this work, supercritical fluid extraction (SFE) coupled with magnetic multi-walled carbon nanotubes coated with copolymer of polyaniline-polythiophene (MWCNTs/FeO@coPANI-PTH) was used for extracting NDMA and NDEA from valsartan and losartan tablets. The extract was analyzed using gas chromatography with mass spectrometry detection (GC/MS). Coupling magnetic solid phase extraction (MSPE) with SFE method (SFE-MSPE-GC/MS) would resolve low preconcentration factor of SFE, lower the detection limit of NAs, and allows using MWCNTs/FeO@coPANI-PTH in solid matrices. The effective parameters on the MSPE and SFE efficiency were optimized using central composite design methods. According to the results of SFE-MSPE-GC/MS under optimized experimental conditions, the limits of detection and limits of quantifications were 0.11-0.15 µg/kg and 0.38-0.50 µg/kg, respectively (RSDs < 6.42 %). This method was validated for acceptance criteria according to ICH Q2 (R1). It could also be developed into other drug substances (DS) that may contain NAs, since in the synthesis and production of different drugs, there is also the possibility of formation or contamination with NAs.