Quantification of a promising JNK inhibitor and nitrovasodilator IQ-1 and its major metabolite in rat plasma by LC-MS/MS.

Autor: Lakeev AP; Goldberg Research Institute of Pharmacology & Regenerative Medicine, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, 634028, Russia.; National Research Tomsk State University, Tomsk, 634050, Russia., Frelikh GA; Goldberg Research Institute of Pharmacology & Regenerative Medicine, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, 634028, Russia., Yanovskaya EA; Goldberg Research Institute of Pharmacology & Regenerative Medicine, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, 634028, Russia., Kovrizhina AR; National Research Tomsk Polytechnic University, Tomsk, 634050, Russia., Udut VV; Goldberg Research Institute of Pharmacology & Regenerative Medicine, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, 634028, Russia.; National Research Tomsk State University, Tomsk, 634050, Russia.
Jazyk: angličtina
Zdroj: Bioanalysis [Bioanalysis] 2022 Nov; Vol. 14 (22), pp. 1423-1441. Date of Electronic Publication: 2023 Jan 27.
DOI: 10.4155/bio-2022-0193
Abstrakt: Background: IQ-1 is a promising c-Jun-N-terminal kinase inhibitor and nitrovasodilator. An LC-MS/MS method was validated to determine IQ-1 isomers and major metabolite IQ-18 in rat plasma. Materials & methods: The analytes were extracted using ethyl acetate. The chromatographic separation was performed on a C8 column (150 × 4.6 mm, 5 μm) under acetonitrile-water (5 mM ammonium formate buffer, pH 2.93) gradient elution. Multiple reaction monitoring was used for MS/MS detection in the positive ion mode. Results: The method was fully validated over the range of 0.1-400 ng/ml ( Z -isomer), 0.9-3600 ng/ml ( E -isomer), 5.0-4000 (IQ-18). Conclusion: This method has been successfully applied to pharmacokinetic studies of IQ-1 and IQ-18 in rats after a single oral dose of IQ-1 (50 mg/kg).
Databáze: MEDLINE