Pharmacokinetics, biodistribution and excretion studies of neotuberostemonine, a major bioactive alkaloid of Stemona tuberosa

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 5 mM 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 11.37 ng/mL and 17.68 ng·h/mL at 20 mg/kg and 137.6 ng/mL and 167.4 ng·h/mL at 40 mg/kg, and the t1/2 were 2.28 and 3.04 h at 20 and 40 mg/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.

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