Determination of IQZ23 in rat plasma using LC-MS/MS: consideration for matrix effect and internal standard interference.

Aim: IQZ23, a novel β-indoloquinazoline derivative, is a potential therapeutic agent for obesity and related metabolic disorders. To assist pharmacokinetics evaluation, a quantitative method for IQZ23 in rat plasma is required. Methods & Results: An LC-MS/MS assay for the determination of IQZ23 in rat plasma was developed and validated for the first time. Chromatographic conditions were optimized to ameliorate matrix effect with direct monitoring of typical phospholipids, including phosphatidylcholine and lysophosphatidylcholine. The structural analog internal standard (SYSU-3d) was set at a proper concentration to avoid analyte sensitivity loss caused by internal standard interference. The well-validated method was employed in the pharmacokinetics study of IQZ23 in Sprague-Dawley rats. Conclusion: This study provided valuable references for the further preclinical study of IQZ23.