Comparative analysis of pharmacokinetics of vancomycin hydrochloride in rabbits after ocular, intragastric, and intravenous administration by LC-MS/MS

The objective of this study was to compare the pharmacokinetics of vancomycin hydrochloride administered into rabbits through different routes and explore the feasibility of peptide drugs entering the systemic circulation through ocular administration.A convenient, accurate, and rapid liquid chromatography-trandem mass spectrometric (LC-MS/MS) method was established and used for the determination of vancomycin hydrochloride in rabbit plasma after intravenous administration (1.5 mg/kg), intragastric, and ocular administration (15 mg/kg). The pharmacokinetic parameters were analyzed using the DAS 2.0 software.We obtained a linear calibration curves vancomycin hydrochloride in plasma of rabbits over a concentration range of 0.05–10.0 μg/mL (R2 > 0.9995), the interassay accuracy was within 5%, precision of 1.66–3.38%, and recovery of >85%. No matrix effects were observed. The absolute bioavailability of vancomycin hydrochloride after intragastric and ocular administration was 1.0 and 7.3%, with the half-life values of 63.1 and 138.5 min, respectively.Therefore, the LC-MS/MS method established in this experiment was suitable for the determination of vancomycin hydrochloride. Vancomycin hydrochloride was rapidly absorbed into the blood circulation after ocular administration. Ocular administration was linked to higher bioavailability compared with intragastric administration, suggesting that the former will become a route for the delivery of peptide drugs.