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Sensitive CE‐MS method for monitoring of riociguat and desmethylriociguat levels in human serum
Author(s) -
Hložek Tomáš,
Štícha Martin,
Bursová Miroslava,
Jelínek Ivan,
Tůma Petr,
Čabala Radomír
Publication year - 2020
Publication title -
electrophoresis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.666
H-Index - 158
eISSN - 1522-2683
pISSN - 0173-0835
DOI - 10.1002/elps.202000135
Subject(s) - riociguat , capillary electrophoresis , chromatography , analyte , chemistry , pharmacokinetics , mass spectrometry , ammonium formate , calibration curve , detection limit , resolution (logic) , pharmacology , guanylate cyclase , medicine , biochemistry , receptor , computer science , artificial intelligence
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.