Recently, N-nitrosamines have been unexpectedly found in generic sartan products. Herein, we developed a sensitive and stable GC-MS/MS method with multiple reactions monitoring mode for the simultaneous determination of four N-nitrosamines in sartan substances, namely, N-nitrosodimethylamine, N-nitrosodiethylamine, N-nitrosodibutylamine, and N-nitrosodiisopropylamine. The conditions of gas chromatography and mass spectrometry were optimized. The method was validated according to the International Council for Harmonization guidelines in terms of sensitivity, linearity, accuracy, precision, specificity, and stability. The limits of detection of N-nitrosamines in sartan substances ranged from 0.002 to 0.150 ppm, and the corresponding limits of quantification were in the range of 0.008-0.500 ppm, which met the sensitivity requirements for the limits set by the Food and Drug Administration of the United States. The internal standard curve of four N-nitrosamines showed good linearity of regression coefficients over 0.99. The recoveries of N-nitrosamines in selected sartan drugs ranged from 87.68 to 123.76%. The intraday and interday relative standard deviation values were less than 9.15%. Therefore, this proposed method exhibited good sensitivity and precision, high accuracy, and fast analysis speed, which provide a reliable method for quality control of N-nitrosamines in sartan products.

Systematic investigation of cyproconazole, including absolute stereochemistry, fungicidal activity, quantification in two matrixes, and stereoselective degradation in cucumber, are conducted in this study. By virtue of vibrational circular dichroism (VCD) spectroscopy, absolute configurations of four stereoisomers were identified to be (2R,3R)-(+)-, (2R,3S)-(+)-, (2S,3S)-(−)-, and (2S,3R)-(−)-cyproconazoles. Then four stereoisomers exhibited stereoselective fungicidal activities against Fusarium graminearum Schw and Magnaporthe oryzae, and the order of fungicidal activity was (2S,3S)-(−)-stereoisomer > the stereoisomer mixture > (2S,3R)-(−)-stereoisomer > (2R,3R)-(+)-stereoisomer > (2R,3S)-(+)-stereoisomer. Moreover, chiral liquid chromatography-tandem mass spectrometry was used to identify and quantify cyproconazole stereoisomers in soil and cucumber matrixes. Good linearity (R 2 ≥ 0.99) and recoveries (86.79−92.47%, RSD ≤ 3.94%) for them were achieved, individually. Furthermore, stereoselective degradation of four cyproconazole stereoisomers was observed in cucumber and the order of degradation rate was (2R,3R)-(+)-cyproconazole > (2S,3S)-(−)-cyproconazole > (2R,3S)-(+)-cyproconazole > (2S,3R)-(−)-cyproconazole. We envision that such systematic assessments of chiral fungicides at an enantiomeric level would provide valuable information in future studies involving enantioselective physiological, metabolic, and toxicological activities.

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N-nitroso-N-methyl-4-aminobutyric acid (NMBA) is the third N-nitrosamine impurity found in sartans. Herein, a sensitive and stable LC-MS/MS method with multiple reactions monitoring mode has been developed for the quantitative determination of NMBA in four sartan substances. The effective separation of NMBA and sartan substances was achieved on a C18 column under gradient elution conditions. The mass spectrometry method of the atmospheric pressure chemical ionization source and internal standard method was selected as the quantitative analysis method of NMBA. Then, this proposed LC-MS/MS analysis method was validated in terms of specificity, sensitivity, linearity, accuracy, precision and stability. Good linearity with correlation coefficient over 0.99 was obtained at the NMBA concentration of 3–45 ng/mL, and the limit of quantification was 3 ng/mL. Additionally, the recoveries of NMBA in four sartan substances ranged from 89.9% to 115.7%. The intra-day and inter-day relative standard deviation values were less than 5.0%. In conclusion, this developed determination method for NMBA through liquid chromatography–tandem mass spectrometry showed the characteristics of good sensitivity, high accuracy and precision, which will be of great help for the quantitative analysis of NMBA in sartan products.