Analysis and stability of a novel anticancer agent, SJ-8029, possessing microtubule and topoisomerase inhibiting activities

This report describes a simple and sensitive isocratic high-performance liquid chromatography with UV detection for the analysis of a novel antineoplastic agent, SJ-8029 in rat serum. The analysis utilized a Merck Lichrocart RP-8 analytical column and a mobile phase consisting of acetonitrile: 0.1% triethylamine in deionized water (55: 45, v/v). SJ-8029 was extracted from serum by one-step extraction with tert-butyl methyl ether. SJ-8029 was eluted at 12.7 min at a mobile phase flow rate of 1 mL/min. The standard curve was linear (r² = 0.9999) over the concentration range of 5-10,000 ng/mL. The extraction recovery for SJ-8029 was > 89.4% and the intra- and inter-day assay variability of SJ-8029 ranged from 3.9-18.8% and 4.5-18.4%, respectively. The LOD and LOQ were 1 and 5 ng/mL, respectively, using a serum sample volume of 100 μL. The developed assay method was applied to a pharmacokinetic study after i.v. injection of SJ-8029 to rats at a dose of 8 mg/kg. In addition, the stability of SJ-8029 was assessed in serum as a function of temperature, and the formation of degradation products M1, M2 and M3 was determined by HPLC with fluorescence detection. Further analysis by LC/MS/MS showed that SJ-8029 was degraded in serum to microtubule and topoisomerase inhibiting components.