Rapid and selective determination of 9 nitrosamines in biological samples using ultra-high performance liquid chromatography-triple quadrupole linear ion trap mass spectrometry
A sensitive, selective and convenient method for the simultaneous determination of 9 nitrosamines (NAs) in biological samples was developed using isotope dilution ultra-high performance liquid chromatography-triple quadrupole linear ion trap mass spectrometry (UPLC-QTRAP-MS). Multiple reaction monitoring-information dependent acquisition-enhanced product ion (MRM-IDA-EPI) scan mode was performed to eliminate false positive results, and the whole detection procedure was characterized by less time consuming and simple sample preparation. 9 NAs were separated through a T3 column with the gradient elution of acetonitrile and water, and detected by UPLC-QTRAP-MS with an atmospheric pressure chemical ionization (APCI) source in the positive mode. The quantitative analysis was carried out via the isotope internal standard method with a matrix calibration curve. Under the optimized conditions, good linearity for the 9 NAs was achieved in the range of 0.2–20 μg L−1 with correlation coefficients (r) higher than ≥0.9991, and the limits of detection and limits of quantitation were 0.02–0.1 μg L−1 (S/N = 3) and 0.06–0.3 μg L−1 (S/N = 10), respectively. Satisfactory recoveries ranging from 79.4% to 108.0% were obtained, and the precision of the proposed method, indicated by the relative standard deviations (RSDs), was 2.3–12.9%. The matrix effect study showed that NDMA, NMOR and NMEA presented a matrix suppression effect, NDPHA displayed a matrix enhancement effect, and the matrix effects of the other 5 analytes could be ignored. Real application of the developed method in 13 urine and 24 plasma samples demonstrated that NDBA, NPIP and NPYR occurred in both urine and plasma samples with the concentration of 0.038–0.60 μg L−1, while other NAs were not detected. Such a method was sensitive and selective, and could be applied to the rapid qualitative and quantitative analysis of the 9 NAs in biological samples.