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

Abstract

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).