Preclinical pharmacokinetic study of a new thiazolyl hydrazone derivative with antifungal activity in mice plasma by LC-MS/MS.

RN104, named 2-[2-(cyclohexylmethylene)hydrazinyl)]-4-phenylthiazole, is a thiazolyl hydrazone derivative with promising antifungal activity. Pharmacokinetic profile of the RN104 was evaluated in mice plasma using a developed and validated bioanalytical method by LC-MS/MS. Clotrimazole was used as internal standard. The analytes were extracted by a protein precipitation procedure and separated on a C18 end-capped column and mobile phase composed of acetonitrile - 0.1% formic acid (85:15, v/v), in isocratic mode. Electrospray ionization in positive ionization mode (ESI + ) and multiple reaction monitoring (MRM) were employed using the transitions m/z 286.1 → m/z 176.1 (quantifier) and m/z 286.1 → m/z 112.2 (qualifier) for RN104 and m/z 345.2 → m/z 277.1 (quantifier) and m/z 345.2 → m/z 165.2 (qualifier) for internal standard. The method was validated and proved to be linear, accurate, precise, and selective over the range 0.625 to 40.0 ng/mL. The pharmacokinetic model that best fit the data was the bicompartmental model. The maximum plasmatic concentration was reached 20 min after administration (per os and intraperitoneal) and the highest plasma concentration of RN104 was found after per os administration at a dosage of 50 mg/kg compared to i.p. administration at 10 mg/kg.