Neotuberostemonine is a potent antitussive alkaloid extracted from Stemona tuberosa. However, the pharmacokinetics, tissue distribution and excretion of pure neotuberostemonine have not been reported. The present study was aimed to investigate the pharmacokinetic parameters of neotuberostemonine by developing an ultra-high performance liquid chromatography-tandem mass spectrometry method. Neotuberostemonine and tetrahydropalmatine (internal standard, IS) in bio-samples were extracted by protein precipitation with methanol and successfully separated on a Zorbax Extend C18 column by using a mobile phase of acetonitrile and a mixture of 0.1% formic acid and 5mM ammonium acetate. The detection was performed by using positive ion electrospray ionization in multiple reaction monitoring mode. The MS/MS ion transitions were monitored at m/z 376.1→302.0 for neotuberostemonine and 355.8→192.0 for IS. After oral administration of neotuberostemonine in rats, the Cmax and AUC0-∞ were 11.37ng/mL and 17.68ng·h/mL at 20mg/kg and 137.6ng/mL and 167.4ng·h/mL at 40mg/kg, and the t1/2 were 2.28 and 3.04h at 20 and 40mg/kg, respectively. The high neotuberostemonine concentrations were found in intestine, stomach and liver, and there was no long-term accumulation of neotuberostemonine in tissues. Total recoveries of neotuberostemonine were only 0.90% (0.19% in bile, 0.05% in urine and 0.66% in feces), which might be resulted from the intestine and liver first-pass effects, indicating that neotuberostemonine may be mainly excreted as its metabolites. All above results would provide helpful information for the further pharmacological and clinical studies of neotuberostemonine and the crude drug.

中文翻译：

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Neotuberostemonine的药代动力学，生物分布和排泄研究。

Neotuberostemonine是一种有效的镇咳生物碱，从Stemona tuberosa提取。但是，尚未报道纯新结核菌灵的药代动力学，组织分布和排泄。本研究旨在通过开发一种超高效液相色谱-串联质谱法研究新结核菌灵的药代动力学参数。用甲醇通过蛋白质沉淀法提取生物样品中的新结核铁门汀和四氢巴马汀（内标，IS），并使用乙腈和0.1％甲酸与5mM乙酸铵的混合物在Zorbax Extend C18色谱柱上成功分离。通过在多个反应监测模式下使用正离子电喷雾电离进行检测。在m / z 376.1→302处监测MS / MS离子跃迁。新沙丁胺酸为0，IS为355.8→192.0。在大鼠中口服新结核菌灵后，Cmax和AUC0-∞在20mg / kg时分别为11.37ng / mL和17.68ng·h / mL，在40mg / kg时分别为137.6ng / mL和167.4ng·h / mL，t1 / 2在20和40mg / kg下分别为2.28和3.04h。在肠，胃和肝脏中发现了新的结核菌丁胺高浓度，并且组织中没有长期的新结核菌丁胺积累。新结核菌素的总回收率仅为0.90％（胆汁为0.19％，尿液为0.05％，粪便为0.66％），这可能是由于肠道和肝脏的首过效应所致，这表明新结核菌素可能主要以代谢产物的形式排泄。以上所有结果将为新结核铁蛋白及其原料药的进一步药理和临床研究提供有益的信息。