GB Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, Vladivostok 690022, Russia.
Eur J Pharm Sci. 2013 Jul 16;49(4):461-7. doi: 10.1016/j.ejps.2013.05.017. Epub 2013 May 30.
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.
测定了免疫缺陷疾病中药物先导化合物 Cumaside 的主要化合物葫芦苦素 A2-2 型三萜糖苷在小鼠脾脏中的分布。为此，使用放射光谱法、MALDI-MS 和 MALDI 成像质谱法（IMS）分别研究了 Balb/c 小鼠脾组织匀浆中糖苷含量随时间的稳定性和动态变化，以及葫芦苦素 A2-2 在组织切片中的空间分布。在单次腹腔内（i.p.）注射 5mg/kg 的剂量后，MALDI-MS 可可靠地检测到小鼠脾脏组织中的葫芦苦素 A2-2。糖苷在脾脏中稳定，在 i.p.注射后 24 小时内，无论是在组织匀浆中还是在完整器官中，都不会发生代谢转化。葫芦苦素 A2-2 的吸收相当迅速：在注射后 30 分钟内即可观察到组织匀浆中糖苷的最大浓度（Cmax）；在 3 小时时记录到最低值。这些结果与（3）H-葫芦苦素 A2-2 的药代动力学研究结果一致。通过 MALDI-IMS 确定，糖苷主要位于脾脏的浆膜层部分，而在器官的红髓和白髓中仅检测到少量糖苷。在给药后 15-30 分钟获得的 MALDI MS 图像清楚地反映了器官周围区域的高药物浓度，随后其在表面部分下降，并在脾脏的内部部分重新分配非常轻微。
