Application of capillary electrophoresis-nano-electrospray ionization-mass spectrometry for the determination of N-nitrosodimethylamine in pharmaceuticals
Language English Country Germany Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- Keywords
- Capillary electrophoresis, Mass spectrometry, N-nitrosodimethylamine, Nano-electrospray ionization, Valsartan,
- MeSH
- Dimethylnitrosamine analysis MeSH
- Electrophoresis, Capillary methods MeSH
- Spectrometry, Mass, Electrospray Ionization methods MeSH
- Drug Contamination * MeSH
- Linear Models MeSH
- Nanotechnology MeSH
- Reproducibility of Results MeSH
- Sensitivity and Specificity MeSH
- Tablets MeSH
- Valsartan chemistry MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Dimethylnitrosamine MeSH
- Tablets MeSH
- Valsartan MeSH
After a presence of highly hepatotoxic and potentially carcinogenic N-nitrosodimethylamine was detected in certain lots of sartan, ranitidine, metformin, and other pharmaceuticals, local regulatory authorities issued recalls of suspected products, and concerns of the pharmacotherapy safety were widely discussed. Since then, testing of a representative sample of each produced lot of these pharmaceuticals is required as a part of quality control processes. Hence, an interface-free CE-nanoESI system coupled with MS detection was employed for the development of a simple and economical method for quantitative detection of this contaminant in the valsartan drug substances and finished formulations used as model matrices. In this arrangement, a fused-silica capillary was used as both a separation column and a nanoESI emitter providing high ionization efficiency and sensitivity. The optimized procedure was found to have sufficient selectivity, linearity, accuracy, and precision. The established LOD and LOQ values were 0.3 and 1.0 ng/mL, respectively. The practical applicability of the method was tested by analyses of commercially available Valsacor® tablets. The results obtained prove that the developed procedure represents a promising alternative to currently available GC- and LC-based methods. Furthermore, after an adjustment of the separation conditions, the CE-nanoESI/MS system can be conceptually used for the determination of NDMA in other suspected pharmaceuticals.
Department of Chemistry Seoul National University Seoul Korea
Institute of Analytical Chemistry of the Czech Academy of Sciences v v i Brno Czech Republic
See more in PubMed
Farrukh, M. J., Tariq, M. H., Malik, O., Khan, T. M., Ther. Adv. Drug Saf. 2019, 10, 2042098618823458.
White, C. M., Ann. Pharmacother. 2020, 54, 611-614.
Lim, H. H., Oh, Y. S., Shin, H. S., J. Pharm. Biomed. Anal. 2020, 189, 113460.
Tricker, A. R., Preussmann, R., Mutat. Res. 1991, 259, 277-289.
Knekt, P., Järvinen, R., Dich, J., Hakulinen, T., Int. J. Cancer 1999, 80, 852-856.
Pottegård, A., Kristensen, K. B., Ernst, M. T., Johansen, N. B., Quartarolo, P., Hallas, J., BMJ 2018, 362, k3851.
Masada, S., Tsuji, G., Arai, R., Uchiyama, N., Demizu, Y., Tsutsumi, T., Abe, Y., Akiyama, H., Hakamatsuka, T., Izutsu, K. I., Goda, Y., Okuda, H., Sci. Rep. 2019, 9, 11852.
Choi, J., Valentine, R. L., Water Res. 2002, 36, 817-824.
Rywotycki, R., Meat Sci. 2003, 65, 669-676.
Andrzejewski, P., Nawrocki, J., Water Sci. Technol. 2007, 56, 125-131.
Fristachi, A., Rice, G., J. Water Health 2007, 5, 341-355.
Yurchenko, S., Molder, U., Food Chem. 2007, 100, 1713-1721.
Park, J. E., Seo, J. E., Lee, J. Y., Kwon, H., Toxicol. Res. 2015, 31, 279-288.
Kadmi, Y., Favier, L., Soutrel, I., Lemasle, M., Wolbert, D., Cent. Eur. J. Chem. 2014, 12, 928-936.
Charoo, N. A., Ali, A. A., Buha, S. K., Rahman, Z., AAPS PharmSciTech 2020, 20, 166.
Snodin, D. J., Elder, D. P., Regul. Toxicol. Pharmacol. 2019, 103, 325-329.
Sörgel, F., Kinzig, M., Abdel-Tawab, M., Bidmon, C., Schreiber, A., Ermel, S., Wohlfart, J., Besa, A., Scherf-Clavel, O., Holzgrabe, U., J. Pharm. Biomed. Anal. 2019, 172, 395-405.
Khorol'skii, M. D., Anan'ina, O. V., Chaplenko, A. A., Nedkov, I. V., Maslennikova, N. V., Ramenskaya, G. V., Pharm. Chem. J. 2019, 53, 766-770.
Tsutsumi, T., Akiyama, H., Demizu, Y., Uchiyama, N., Masada, S., Tsuji, G., Arai, R., Abe, Y., Hakamatsuka, T., Izutsu, K. I., Goda, Y., Okuda, H., Biol. Pharm. Bull. 2019, 42, 547-551.
Schmidtsdorff, S., Schmidt, A. H., J. Pharm. Biomed. Anal. 2019, 174, 151-160.
Alshehri, Y. M., Alghamdi, T. S., Aldawsari, F. S., J. Pharm. Biomed. Anal. 2020, 191, 113582.
Štěpánová, S., Kašička, V., J. Sep. Sci. 2014, 37, 2039-2055.
El Deeb, S., Wätzig, H., Abd El-Hady, D., Albishri, H. M., Sänger-van de Griend, C., Scriba, G. K. E., Electrophoresis 2014, 35, 170-189.
El Deeb, S., Wätzig, H., Abd El-Hady, D., Sänger-van de Griend, C., Scriba, G. K. E., Electrophoresis 2016, 37, 1591-1608.
Görög, S., TrAC Trends Anal. Chem. 2018, 101, 2-16.
Zhu, Q., Scriba, G. K. E., J. Pharm. Biomed. Anal. 2018, 147, 425-438.
Řemínek, R., Foret, F., Electrophoresis 2021, 42, 19-37.
Juraschek, R., Dülcks, T., Karas, M., J. Am. Soc. Mass Spectrom. 1999, 10, 300-308.
Sanz-Nebot, V., Balaguer, E., Benavente, F., Barbosa, J., Electrophoresis 2005, 26, 1457-1465.
Page, J. S., Kelly, R. T., Tang, K., Smith, R. D., J. Am. Soc. Mass Spectrom. 2007, 18, 1582-1590.
Höcker, O., Montealegre, C., Neusüß, C., Anal. Bioanal. Chem. 2018, 410, 5265-5275.
Tycova, A., Foret, F., J.Chromatogr. A 2015, 1388, 274-279.
Tycova, A., Vido, M., Kovarikova, P., Foret, F., J. Chromatogr. A 2016, 1466, 173-179.
Tycova, A., Prikryl, J., Foret, F., Electrophoresis 2016, 37, 924-930.
Ng, C. L., Ong, C. P., Lee, H. K., Li, S. F. Y., J. Chromatogr. Sci. 1994, 32, 121-125.
Taga, A., Oura, Y., Suzuki, S., Boki, K., Honda, S., J. Oleo Sci. 2006, 55, 573-577.
Sanches Filho, P. J., Rios, A., Valcárcel, M., Caramão, E. B., Water Res. 2003, 37, 3837-3842.
Sanches Filho, P. J., Rios, A., Valcárcel, M., Zanin, K. D., Caramão, E. B., J. Chromatogr. A 2003, 985, 503-512.
Taga, A., Nishi, T., Honda, Y., Sato, A., Terashima, H., Suzuki, K., Kodama, S., Boki, K., J. Oleo Sci. 2007, 56, 429-434.
Modir-Rousta, A., Bottaro, C. S., Electrophoresis 2013, 34, 2553-2560.
Modir-Rousta, A., Bottaro, C. S., Electrophoresis 2015, 36, 1016-1023.
Wan, H., Holmén, A., Någård, M., Lindberg, W., J. Chromatogr. A 2002, 979, 369-377.
Siddiqui, N., Husain, A., Chaudhry, L., Alam, M. S., Mitra, M., Bhasin, P. S., J. Appl. Pharm. Sci. 2011, 1, 12-19.
