Tacrolimus has a narrow therapeutic index and large individual differences in pharmacokinetics. The distribution of
tacrolimus in ascitic fluid and its influence on whole-blood
tacrolimus were unclear. In this study, a sensitive ultra-performance liquid chromatography-tandem mass spectrometry method was established and validated for the quantification of
tacrolimus in the ascitic fluid of
liver transplant recipients. Chromatographic separation was achieved on an Agilent ZORBAX Eclipse Plus Phenyl-Hexyl column (2.1 × 100 mm, 3.5 μm). Mass spectrometry was performed in multiple reaction monitoring conditions of transitions m/z 821.4→768.5 for
tacrolimus. The concentrations of
tacrolimus in the ascitic fluid range from 0.2 to 3.0 ng/mL, accounting for 1.19-31.87% of whole-blood
tacrolimus concentrations. A linear mixed model showed a statistically significant positive correlation between the steady-state trough blood concentration of
tacrolimus and the corresponding amount of
tacrolimus excreted in the ascitic fluid for 24 consecutive hours, especially after normalization by daily dose per unit
body weight. These data suggested that the distribution of
tacrolimus in the ascitic fluid has great individual differences. The whole-blood
tacrolimus concentration, dose per unit
body weight, and other confounding factors may contribute to the excretion of
tacrolimus in ascitic fluid, but the influence of
tacrolimus excretion in drained ascitic fluid on the whole-blood
tacrolimus concentration is negligible.