A multi-analyte LC-MS/MS method for screening and quantification of nitrosamines in sartans

Authors

Shu-Han Chang, Food and Drug Administration, Ministry of Health and Welfare, Taipei,TaiwanFollow
Ching-Chia Chang, Food and Drug Administration, Ministry of Health and Welfare, Taipei,TaiwanFollow
Li-Jing Wang, Food and Drug Administration, Ministry of Health and Welfare, Taipei,TaiwanFollow
Wei-Ching Chen, Food and Drug Administration, Ministry of Health and Welfare, Taipei,TaiwanFollow
Shu-Yu Fan, Food and Drug Administration, Ministry of Health and Welfare, Taipei,TaiwanFollow
Chi-Zong Zang, Food and Drug Administration, Ministry of Health and Welfare, Taipei,TaiwanFollow
Ya-Hui Hsu, Food and Drug Administration, Ministry of Health and Welfare, Taipei,TaiwanFollow
Mei-Chih Lin, Food and Drug Administration, Ministry of Health and Welfare, Taipei,TaiwanFollow
Su-Hsiang Tseng, Food and Drug Administration, Ministry of Health and Welfare, Taipei,TaiwanFollow
Der-Yuan Wang, Food and Drug Administration, Ministry of Health and Welfare, Taipei,TaiwanFollow

Keywords

Carcinogens, Liquid chromatography, Mass spectrometry, Nitrosamines, Sartans

Abstract

An incident of sartan medicine contamination was notified by Europe in June 2018. The contaminant was identified as a probable carcinogenic nitrosamine and the recalls of sartan medicines were soon made. Since then, more nitrosamine contaminants in sartan medicines were reported. To broaden the applicability and variety in nitrosamine determination, a multi-analyte method is required. In this study, a feasible and sensitive multi-analyte LC-MS/MS method for determination of 12 nitrosamines in sartans was established, where the active pharmaceutical ingredients and final products merchandised in Taiwan were also examined. Chromatographic separation was achieved on an Xselect® HSS T3 column (15 cm £ 3 mm i.d., 3.5 mm) with gradient elution using mobile phase A consisting of 0.1% formic acid in water and mobile phase B consisting of 0.1% formic acid in acetonitrile/methanol (2:8). Validation of the proposed method was also carried out. The limit of detection and limit of quantification for 12 nitrosamines were 20 ng/g and 50 ng/g, respectively. The intra-day and inter-day recoveries of nitrosamines were among 80e120% with precision of 20% for most nitrosamines within sartans matrices. The method was successfully established and applied to authentic samples which a total of 98 positive samples containing 5 distinct nitrosamines, including N-nitrosodiethylamine, N-nitrosodimethylamine, N-nitroso-N-methyl-4-aminobutyric acid, N-nitrosomorpholine and Nnitrosopiperidine, were detected from 557 authentic samples.

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Recommended Citation

Chang, Shu-Han; Chang, Ching-Chia; Wang, Li-Jing; Chen, Wei-Ching; Fan, Shu-Yu; Zang, Chi-Zong; Hsu, Ya-Hui; Lin, Mei-Chih; Tseng, Su-Hsiang; and Wang, Der-Yuan (2020) "A multi-analyte LC-MS/MS method for screening and quantification of nitrosamines in sartans," Journal of Food and Drug Analysis: Vol. 28 : Iss. 2 , Article 10.
Available at: https://doi.org/10.38212/2224-6614.1063

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Publisher Note

Due to printer error, this article was previously made available with incorrect page numbers. The article has been repaginated and the article is now available with the correct page numbers for volume 28, issue 2 292-301.