Determination of cucumarioside A2-2 in mouse spleen by radiospectroscopy, MALDI-MS and MALDI-IMS

• Published in: European journal of pharmaceutical sciences Vol. 49; no. 4; pp. 461 - 467
• Main Authors: Pislyagin, E.A., Dmitrenok, P.S., Gorpenchenko, T.Yu, Avilov, S.A., Silchenko, A.S., Aminin, D.L.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 16-07-2013
• Subjects: Animals; Female; Holothurians; Immunomodulatory activity; MALDI-MS and MALDI Imaging Mass Spectrometry; Mass Spectrometry - methods; Mice; Mice, Inbred BALB C; Pharmacokinetic; Saponins - administration & dosage; Saponins - pharmacokinetics; Spectrum Analysis - methods; Spleen - metabolism; Triterpene glycosides; Tritium; Triterpene glycosides; Immunomodulatory activity; MALDI-MS and MALDI Imaging Mass Spectrometry; Holothurians; Pharmacokinetic
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2013.05.017

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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 5mg/kg. The glycoside is stable in the spleen and does not undergo metabolic transformation in either tissue homogenates or in the intact organ within 24h 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 30min after injection; the minimum values were registered in 3h. These results are in agreement with those obtained in the pharmacokinetic study of 3H-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 15–30min 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.