Sensitive CE-MS method for monitoring of riociguat and desmethylriociguat levels in human serum
Jazyk angličtina Země Německo Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
260531/SVV/2020
Charles University project - International
GAUK 11920
Charles University project - International
GAUK - International
SVV - International
PubMed
32640044
DOI
10.1002/elps.202000135
Knihovny.cz E-zdroje
- Klíčová slova
- Capillary electrophoresis, Desmethylriociguat, Determination, Mass spectrometry, Riociguat,
- MeSH
- elektroforéza kapilární metody MeSH
- elektrolyty MeSH
- extrakce kapalina-kapalina MeSH
- hmotnostní spektrometrie s elektrosprejovou ionizací metody MeSH
- lidé MeSH
- limita detekce MeSH
- lineární modely MeSH
- pyrazoly krev chemie izolace a purifikace farmakokinetika MeSH
- pyrimidiny krev chemie izolace a purifikace farmakokinetika MeSH
- reprodukovatelnost výsledků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- elektrolyty MeSH
- pyrazoly MeSH
- pyrimidiny MeSH
- riociguat MeSH Prohlížeč
Riociguat is novel antihypertensive drug for treatment of pulmonary hypertension. As such, it is still being tested in many clinical and pharmacokinetic trials. Existing methods that determine serum riociguat and desmethylriociguat (DMR) are based solely on liquid chromatography with mass spectrometry. Therefore, we present a novel capillary electrophoresis with mass spectrometry method (CE-MS) for their determination in human serum as alternative method for ongoing trials. Complete resolution of both analytes was achieved by means of pH optimization of ammonium formate background electrolytes that are fully compatible with ESI/MS detection. Simple liquid-liquid extraction was used as sample pretreatment. The calibration dependence of the method was linear (in the range of 10-1000 ng/mL), with adequate accuracy (90.1-114.9%) and precision (13.4%). LOD and LOQ were arbitrarily set at 10 ng/mL for both analytes. Clinical applicability was validated using serum samples from patients treated with riociguat in pharmacokinetic study and the results corresponded with reference HPLC-MS/MS values. Capillary electrophoresis proved to be sensitive and selective tool for the analysis of riociguat and DMR.
Department of Analytical Chemistry Faculty of Science Charles University Prague Czech Republic
Department of Hygiene 3rd Faculty of Medicine Charles University Prague Czech Republic
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