Pharmacokinetics and bioavailability of ricolinostat in mouse plasma by UPLC-MS/MS

Abstract Ricolinostat (ACY-1215), a selective Histone Deacetylase 6 (HDAC6) inhibitor, exhibits potent antitumor activity against a broad spectrum of tumors. UPLC-MS/MS technique was employed to identify ACY-1215 in mouse plasma and investigate its pharmacokinetic variations following oral (10 and 30 mg kg −1 ) and intravenous (5 mg kg −1 ) administration. Protein precipitation method utilizing acetonitrile as the solvent and cilostazol as the internal standard (IS) was used for plasma preparation. Chromatographic separation was achieved using an UPLC High Strength Silica (HSS) T3 column with gradient elution employing acetonitrile and 0.1% formic acid in water mobile phase. The linear range of the ACY-1215 standard curve spanned from 0.5 to 1,000 ng mL −1 , exhibiting excellent linearity. Intra-day and inter-day precision were both below 10%, while accuracy ranged from 90 to 108%. Matrix effect fell within the range of 104 to 108%, with recovery exceeding 92%. The bioavailability of ACY-1215 was determined to be 54.4 and 48.4% after oral administration at doses of 10 and 30 mg kg −1 , respectively. The pharmacokinetics of ACY-1215 were successfully evaluated using the UPLC-MS/MS method.