Bio-distribution and pharmacokinetics of nobiliside A-loaded liposome following intravenous administration in rats

• LC/MS/MS is established for biodistribution and pharmacokinetics of Nobliside A.
• Biodistribution and pharmacokinetics of Nobliside A and its liposome are compared.
• Nobliside A and its liposome eliminate slowly in rat after intravenous injection.
• Similar behavior of Nobliside A and its liposome appears in whole blood of rat.
• Nobliside A liposome shows much higher AUC in liver and spleen than its solution.

Nobiliside A (Nob) is a new triterpenoid saponin separated from Holothuria noblilis. In this article, a liquid chromatography–electrospray ionization-tandem mass spectrometry method was established to quantify Nob, a hemolytic saponin, in rat blood and tissue homogenates. Standard curves were linear (r = 0.9988–0.9995) over the range 50–5000 ng/mL in blood and 100–10000 ng/g in tissues. The lower limit of quantification (LLOQ) was 50 ng/mL for Nob. The novel method was rapid, accurate, highly sensitive and highly selective. Using this method, the pharmacokinetics and biodistribution of Nob liposome and Nob solution in Sprague-Dawley rats after a single intravenous dose of 1 mg/kg were then investigated. Nob was cleared slowly from circulation. There was no significant difference of the pharmacokinetic parameters in blood between Nob solution and Nob liposome. The highest AUC of Nob was observed in liver for the two groups, followed by spleen, lungs, kidney and heart. Compared with Nob solution, Nob liposome showed much higher AUC in liver and spleen and much lower AUC in kidney, heart and lung, which might be one important reason for the decreased toxicity of Nob.