title: Bio-distribution and pharmacokinetics of nobiliside A-loaded liposome following intravenous administration in rats.
abstract: 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 50-5000ng/mL in blood and 100-10000ng/g in tissues. The lower limit of quantification (LLOQ) was 50ng/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 1mg/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.
authors.affiliation: Department of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China. Electronic address: xyxnb@126.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Department of Pharmaceutical Science, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Chen
authors.affiliation: Shanghai Institute for Food and Drug Control, Shanghai 201203, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Guo
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D047332:Holothuria / Q000737:chemistry; D057230:Limit of Detection; D008081:Liposomes; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000008:administration & dosage* / Q000097:blood / Q000302:isolation & purification / Q000493:pharmacokinetics*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods; D014018:Tissue Distribution
chemical_list: C515791:3-O-xylopyranosylholosta-7,9(11),22,24-tetraene-3,17-diol; D008081:Liposomes; D012503:Saponins
keywords: Bio-distribution; LC/MS/MS; Liposome; Nobiliside A; Pharmacokinetics