Ocular Pharmacokinetic Study of l-Carnosine and N-Acetyl-l-carnosine in Rabbit by Microdialysis Coupled with UPLC-MS-MS

Abstract

In order to provide useful information for rational drug design, the ocular pharmacokinetics of l-carnosine (CAR) and its acetylized prodrug N-acetyl-l-carnosine (NAC) were investigated. The in vivo microdialysis sampling coupled with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) was developed for continuously simultaneous monitoring of CAR and NAC in rabbit aqueous humor. The measured in vitro recoveries of the probe were 61.3% for CAR and 65.8% for NAC, while in vivo recoveries decreased to 43.1% for CAR and 43.0% for NAC, respectively. The method was sensitive with LLOQ 20.5 ng mL−1 for CAR and 20.4 ng mL−1 for NAC. The initial data indicated that the value of C max and AUC(0–∞) of NAC were higher than these of CAR (C max 2305 vs. 1,802 ng mL−1), (AUC(0–∞) 1,337 vs. 1,891 ng h mL−1), which indicated that the NAC exhibited better ocular bioavailability and duration. The method was rapid, specific and sensitive for continuously monitoring of aqueous humor and it was successfully applied to pharmacokinetic studies of CAR and NAC.