Bioequivalence and food effect study of enteric-coated mesalazine tablets in healthy Chinese volunteers by HPLC-ESI-MS/MS.

Objective: To establish a developed HPLC-ESI-MS/MS method for simultaneous determination of mesalazine (5-ASA) and its major metabolite N-Ac-5-ASA in human plasma and to investigate bioequivalence of two enteric-coated mesalazine tablets as well as the effect of high-fat food on the pharmacokinetics of 5-ASA and N-Ac-5-ASA.

Methods: In this open-label, randomized, crossover, two-states, four-period study, 20 healthy Chinese volunteers were randomized to receive a single oral dose of trial or reference preparation (2 × 250 mg) under fasting and fed state. Plasma samples were obtained at 0, 1, 2, 3, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 10, 12, 24, and 36 hours postdose and were measured by a developed HPLC-ESI-MS/MS method. Safety and tolerability were assessed throughout the study.

Results: The HPLC-ESI-MS/MS method required only 7.0 minutes run time and was successfully applied in analyzing ~ 2,000 samples. High-fat-food administration prolonged tmax of 5-ASA and N-Ac-5-ASA (p < 0.05), while AUC was not significantly affected by the meal (p > 0.05). The 90% confidence intervals (CIs) of the fed/fasting and trial/reference ratios of log-transformed Cmax and AUC were within 80-125%. The two one-sided t-tests showed that the trial and reference preparation were bioequivalent (p > 0.05).

Conclusions: This developed HPLC-ESI-MS/MS method is suitable for massive biomedical analysis. Trial and reference preparations are bioequivalent under fasting and fed state. High-fat-food administration delays the absorption of mesalazine while total exposure is not affected. Dietary habits should always be taken into consideration when enteric-coated mesalazine tablets were prescribed to patients.