title: Determination of cucumarioside A₂-2 in mouse spleen by radiospectroscopy, MALDI-MS and MALDI-IMS.
abstract: The distribution of triterpene glycoside cucumarioside A₂-2, the main compound of medical lead Cumaside in immunodeficiency diseases, in mouse spleen was determined. For this purpose the stability and dynamics of glycoside content changes over time in Balb/c mouse spleen tissue homogenate as well as the study of the cucumarioside A2-2 spatial distribution in tissue sections were investigated using radiospectroscopy, MALDI-MS and MALDI Imaging Mass Spectrometry (IMS), correspondingly. Cucumarioside A₂-2 is reliably detected by MALDI-MS in the mouse spleen tissue after single intraperitoneal (i.p.) injection at a dosage of 5 mg/kg. The glycoside is stable in the spleen and does not undergo metabolic transformation in either tissue homogenates or in the intact organ within 24 h after i.p. injection. The cucumarioside A₂-2 was absorbed fairly rapidly: the glycoside maximum concentration (Cmax) in tissue homogenate was observed in the first 30 min after injection; the minimum values were registered in 3 h. These results are in agreement with those obtained in the pharmacokinetic study of (3)H-cucumarioside A₂-2. It was established by MALDI-IMS that glycoside was mainly located in the tunica serosa part of the spleen and only a small amount was detected within the red and white pulp of the organ. MALDI MS images obtained 15-30 min post dosage clearly reflect high drug concentrations in the regions surrounding the organ followed by its decline in the surface part and a very slight redistribution to the internal part of the spleen.
authors.affiliation: GB Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, Vladivostok 690022, Russia. pislyagin@hotmail.com
authors.forename: E A
authors.initials: EA
authors.lastname: Pislyagin
authors.forename: P S
authors.initials: PS
authors.lastname: Dmitrenok
authors.forename: T Yu
authors.initials: TY
authors.lastname: Gorpenchenko
authors.forename: S A
authors.initials: SA
authors.lastname: Avilov
authors.forename: A S
authors.initials: AS
authors.lastname: Silchenko
authors.forename: D L
authors.initials: DL
authors.lastname: Aminin
mesh_terms: D000818:Animals; D005260:Female; D013058:Mass Spectrometry / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D012503:Saponins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013057:Spectrum Analysis / Q000379:methods; D013154:Spleen / Q000378:metabolism*; D014316:Tritium
chemical_list: D012503:Saponins; C539161:cucumarioside A2-2; D014316:Tritium
keywords: Holothurians; Immunomodulatory activity; MALDI-MS and MALDI Imaging Mass Spectrometry; Pharmacokinetic; Triterpene glycosides