Simultaneous determination of six nitrosamines in different pharmaceutical dosage forms by GC-MS/MS with headspace module vs. autosampler solvent vent mode: Development and validation

The determination of N-nitrosamines is of significant importance in pharmaceutical drug products. An analytical method was devised and validated in this study to accurately and easily determine nitrosamines, thereby eliminating the interfering matrix effect in various pharmaceutical forms. N-nitrosodiethylamine (NDEA), N-nitrosodimethylamine (NDMA), N-nitrosodiisopropylamine (NDIPA), N-nitrosomethylphenylamine (NMPA), N-nitrosoisopropylethylamine (NEIPA), and N-nitrosodibutylamine (NDBA) were quantified in the suspension, emulsion, and tablet pharmaceutical forms. The concentration range was adjusted from the quantification limit (QL) to the upper limit of quantification (ULOQ). The limit concentration levels were calculated according to acceptable daily intake of each product and daily limits of N-nitrosamines which mentioned in FDA guidance. The concentration limits were defined to be 1.92 ng/mL, 0.53 ng/mL, 8.0 ng/mL, 30.0 ng/mL, 2.0 ng/mL and 0.53 ng/mL, respectively, for each N-nitrosamines. The method validation was successfully applied with an acceptable linearity (R2 > 0.99), accuracy (recovery range is 79.5-122.4 %) and precision (RSD < 15.0 %). During the analysis, a Gas Chromatography (GC) system with an MS/MS detector and a Headspace (HS) module was employed, equipped with a VF-WAXMS capillary column (30 m × 0.25 mm × 1 μm). The results obtained were compared with a validated GC-MS/MS Autosampler method with solvent vent mode.