Development of a CE-MS method for the study of riociguat and metabolite M1 in pharmaceutical analysis
Language English Country Germany Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
CZ.02.1.01/0.0/0.0/15_003/0000417
Ministry of Education, Youth and Sports - International
- Keywords
- Capillary electrophoresis, Dissociation constant, Fragmentation, Mass spectrometry, Riociguat,
- MeSH
- Electrophoresis, Capillary methods MeSH
- Mass Spectrometry methods MeSH
- Humans MeSH
- Limit of Detection MeSH
- Linear Models MeSH
- Pyrazoles analysis blood chemistry metabolism MeSH
- Pyrimidines analysis blood chemistry metabolism MeSH
- Reproducibility of Results MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Pyrazoles MeSH
- Pyrimidines MeSH
- riociguat MeSH Browser
Riociguat is a novel antihypertensive drug for the treatment of pulmonary hypertension. We present electrophoretic characterization, i.e. migration behavior of riociguat and metabolite M1 as support for optimized CZE/MS assay. Fundamental separation parameters, such as peak width, symmetry, and resolution are studied in a series of ammonium formate buffers within pH range 2.60-5.61. The narrow region of peak symmetry lies close to pH 4.0 for both analytes. Accordingly, the value of resolution maximizes in a background electrolyte adjusted to pH 4.10. Basic calibration parameters estimated from CZE experiments with absorption photometric and mass spectrometric detection of riociguat and metabolite M1 were evaluated. More than three orders lower LOD was achieved with high resolution mass spectrometric detection. The observed difference in the sensitivity of both detection techniques gives priority to the utilization of CZE/MS in practice. The values of dissociation constants of riociguat and metabolite M1, pKBH , were determined from CZE measurements in lithium formate and lithium acetate background electrolytes with constant ionic strength. The value of pKBH = 4.30 ± 0.02 for riociguat corresponds well to the value already presented in the literature. According to our observation, metabolite M1 behaves like a slightly stronger base with estimated pKBH = 4.40 ± 0.02.
See more in PubMed
Riociguat: assessment report, European Medicines Agency, EMA/CHMP/734750/2013.
Conole, D., Scott, L. J., Drugs 2013, 73, 1967-1975.
Garnock-Jones, K. P., Drugs 2014, 74, 2065-2078.
Makowski, C. T., Rissmiller, R. W., Bullington, W. M., Pharmacotherapy 2015, 35, 502-519.
Lian, T. Y., Jiang, X., Jing, Z. C., Drug Des. Devel. Ther. 2017, 11, 1195-1207.
Frey, R., Becker, C., Saleh, S., Unger, S., van der Mey, D., Muck, W., Clin. Pharmacokinet. 2018, 57, 647-661.
Zhang, J., Zhang, X., J. Clin. Exp. Med. 2018, 11, 423-430.
Gnoth, M. J., Hopfe, P. M., Czembor, W., Bioanalysis 2015, 7, 193-205.
Mascherbauer, J., Grunig, E., Halank, M., Hohenforst-Schmidt, W., Kammerlander, A. A., Pretsch, I., Steringer-Mascherbauer, R., Ulrich, S., Lang, I. M., Wargenau, M., Frey, R., Bonderman, D., Wien. Klin. Wochenschr. 2016, 128, 882-889.
Zhou, X., Hu, X., Gu, J., Zhu, J., Acta Cryst. Bs 2017, 73, 891-898.
Ma, R., Li, Z., Di, X., Guo, D., Ji, J., Wang, S., BioSci. Trends 2018, 12, 369-374.
Suntornsuk, L., Anal Bioanal. Chem. 2010, 398, 29-52.
Shanmuganathan, M., Britz-McKibbin, P., Anal. Chim. Acta 2013, 773, 24-36.
El Deeb, S., Watzig, H., El-Hady, D. A., Sanger-van de Griend, C., Scriba, G. K. E., Electrophoresis 2016, 37, 1591-1608.
Frisch, M. J., Trucks, G. W., Schlegel, H. B., Scuseria, G. E., Robb, M. A., Cheeseman, J. R., Scalmani, G., Barone, V., Mennucci, B., Petersson, G. A., Nakatsuji, H., Caricato, M., Li, X., Hratchian, H. P., Izmaylov, A. F., Bloino, J., Zheng, G., Sonnenberg, J. L., Hada, M., Ehara, M., Toyota, K., Fukuda, R., Hasegawa, J., Ishida, M., Nakajima, T., Honda, Y., Kitao, O., Nakai, H., Vreven, T., Montgomery, Jr., J. A., Peralta, J. E., Ogliaro, F., Bearpark, M., Heyd, J. J., Brothers, E., Kudin, K. N., Staroverov, V. N., Kobayashi, R., Normand, J., Raghavachari, K., Rendell, A., Burant, J. C., Iyengar, S. S., Tomasi, J., Cossi, M., Rega, N., Millam, J. M., Klene, M., Knox, J. E., Cross, J. B., Bakken, V., Adamo, C., Jaramillo, J., Gomperts, R., Stratmann, R. E., Yazyev, O., Austin, A. J., Cammi, R., Pomelli, C., Ochterski, J. W., Martin, R. L., Morokuma, K., Zakrzewski, V. G., Voth, G. A., Salvador, P., Dannenberg, J. J., Dapprich, S., Daniels, A. D., Farkas, O., Foresman, J. B., Ortiz, J. V., Cioslowski, J., Fox, D. J., Gaussian 16, Revision C.01, Gaussian Inc., Wallingford, CT, 2016.
Jaroš, M., Hruška, V., Štědrý, M., Zusková, I., Gaš, B., Electrophoresis 2004, 25, 3080-3085.
Poole, S. K., Patel, S., Dehring, K., Workman, H., Poole, C. F., J. Chromatogr. A 2004, 1037, 445.
Koval, D., Kašička, V., Zusková, I., Electrophoresis 2005, 26, 3221-3231.
Zusková, I., Novotná, A., Včeláková, K., Gaš, B., J. Chromatogr. B 2006, 841, 129-134.
Lewars, E. G., Computational Chemistry: Introduction to the Theory and Applications of Molecular and Quantum Mechanics, Springer, 2010.
Wright, P., Alex, A., Nyaruwata, T., Parsons, T., Pullen, F., Rapid Commun. Mass Spectrom. 2010, 24, 1025-1031.
Joyce, J. R., Richards, D. S., J. Am. Soc. Mass Spectrom. 2011, 22, 360-368.
