•The compound 83b1 has the potential to develop as a novel anti- esophageal cancer drug for its high anti-tumor activity and low cytotoxicity.•[J1] A simple, rapid and sensitive method for determination of 83b1 in rat plasma using UHPLC–MS/MS was developed and validated for the first time.•The validated method was employed to study the bioavailability of 83b1 in rat by dosing with intravenous injection (1 mg/kg) and gavage (10 mg/kg).Great attentions have been drawn by quinoline for its broad bioactivity as anti-fungal, anti-bacterial and anti-tumor activities. Compared with cisplatin, 83b1, a quinoline derivative, showed equal activity in anti-tumor and lower cyctotoxicity in normal cell. In this study, a simple, rapid and sensitive method for determination of 83b1 in rat plasma using UHPLC–MS/MS was developed for the first time. Loratadine was used as an internal standard (IS). Separation was performed on an Xterra MS C18 column by isocratic elution using acetonitrile: water solution with 1‰ formic acid (90:10, v/v) as mobile phase at a flow rate of 0.3 mL/min. A triple quadrupole mass spectrometer operating in the positive ion-switching electron spray ionization mode with selection reaction monitoring (SRM) was employed to determine 83b1 and IS transitions of m/z 321.82 → 147.84, 382.71 → 258.76 for 83b1 and Loratadine, respectively. The values of specificity, linearity and lower limit of quantification, intra- and inter- day precision and accuracy, extraction recovery, matrix effect and stability for this method satisfied the acceptable limits. The lower limit of quantification was 0.5 ng/mL with a linear range of 0.5–1500 ng/mL. The validated method was employed to study the bioavailability of 83b1 in rat by dosing with intravenous injection (1 mg/kg) and gavage (10 mg/kg), and the oral bioavailability of 83b1 in rat was calculated as 20.9 ± 8.8%.

•A UPLC-MS/MS method for the determination of AKI603 in rat plasma has been firstly developed and validated.•The method has been used to the bioavailability study of AKI603 administered to rats.•The result suggests the potential for AKI603 developed as an orally administered drug.A simple, sensitive and accurate ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of AKI603 in rat plasma has been firstly developed and validated. After a simple liquid–liquid extraction (LLE) with ethyl acetate, the analytes were separated on C18 column (2.1 × 100 mm, 1.9 μm, Thermo) by gradient elution with mobile phase of water (A) (containing 5 mM ammonium acetate and 0.1% formic acid) and methanol (B) with a flow rate of 0.3 mL min−1 and then analyzed by mass spectrometry in the positive multiple reactions monitoring (MRM) mode. The mass transitions monitored were m/z 410.0 → 352.9, m/z 457.1 → 367.9 for AKI603 and internal standard (Ly-7z), respectively. The developed method was validated for specificity, linearity and lower limit of quantification, intra- and inter-day precision and accuracy, extraction recovery, matrix effect and stability whose values satisfied the acceptable limits. The calibration curves for AKI603 was linear in concentration ranges of 0.025–5000 ng mL−1. The method has been successfully used to the bioavailability study of AKI603 administered to rats intravenously (2.5 mg/kg) or orally (25 mg/kg). The oral bioavailability of AKI603 in rats was calculated as 28.7 ± 9.7%.