Development and Validation of an Lc-MS/MS Method for the Pre-Clinical Pharmacokinetic Investigation of the Anticancer Candidate Ac04 in Rodents

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A liquid chromatography-tandem mass spectrometry method was developed for accurate quantification of the acridinic anticancer candidate AC04 (5-acridin-9-ylmethylene-3-(4-methyl-benzyl)-thiazolidine-2,4-dione) in rat plasma viewing the drug's pre-clinical pharmacokinetic investigation. The sample purification was performed by protein precipitation technique with acetonitrile, and terbinafine was used as the internal standard (IS). The chromatographic separation was achieved using an isocratic mobile phase consisting of a mixture of acetonitrile and 0.1% formic acid, (95:5, v/v) flowing through an ACE® C18 column (5 µm, 2.1 × 50 mm) at a flow rate of 0.45 mL/min. Mass spectrometer with electrospray ionization (ESI) monitored, in positive mode, the transitions m/z 411.1 > 104.8 and 292.4 > 142 for AC04 and internal standard, respectively. An extensive method validation was carried out in accordance with Food and Drug Administration (FDA) guidelines. The method showed linearity in the concentration range of 2.5–500.0 ng/mL with correlation coefficient 0.993. Intra- and inter-day precision were less than 8.5 and 3.7%, respectively. The applicability of the method for pharmacokinetic investigation was determined in a pilot investigation of AC04 plasma profiles after a 1.5 mg/kg intravenous administration to rats.