title: Pharmacokinetics, biodistribution and excretion studies of neotuberostemonine, a major bioactive alkaloid of Stemona tuberosa.
abstract: 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.
authors.affiliation: State Key Laboratory of Natural Medicines, Research Department of Pharmacognosy, China Pharmaceutical University, 639# Longmian Road, Nanjing 211198, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Natural Medicines, Research Department of Pharmacognosy, China Pharmaceutical University, 639# Longmian Road, Nanjing 211198, PR China.
authors.forename: Liting
authors.initials: L
authors.lastname: Ou
authors.affiliation: State Key Laboratory of Natural Medicines, Research Department of Pharmacognosy, China Pharmaceutical University, 639# Longmian Road, Nanjing 211198, PR China.
authors.forename: Dong
authors.initials: D
authors.lastname: Han
authors.affiliation: State Key Laboratory of Natural Medicines, Research Department of Pharmacognosy, China Pharmaceutical University, 639# Longmian Road, Nanjing 211198, PR China.
authors.forename: Yongbin
authors.initials: Y
authors.lastname: Tong
authors.affiliation: State Key Laboratory of Natural Medicines, Research Department of Pharmacognosy, China Pharmaceutical University, 639# Longmian Road, Nanjing 211198, PR China. Electronic address: mianzhang@126.com.
authors.forename: Mian
authors.initials: M
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural Medicines, Research Department of Pharmacognosy, China Pharmaceutical University, 639# Longmian Road, Nanjing 211198, PR China.
authors.forename: Xianghong
authors.initials: X
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Natural Medicines, Research Department of Pharmacognosy, China Pharmaceutical University, 639# Longmian Road, Nanjing 211198, PR China. Electronic address: njchaofeng@126.com.
authors.forename: Chaofeng
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000470:Alkaloids / Q000493:pharmacokinetics*; D000818:Animals; D001646:Bile / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D004365:Drugs, Chinese Herbal / Q000493:pharmacokinetics; D005243:Feces / Q000737:chemistry; D007422:Intestines / Q000737:chemistry; D007783:Lactones / Q000493:pharmacokinetics*; D008099:Liver / Q000737:chemistry; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D041901:Stemonaceae / Q000737:chemistry*; D013270:Stomach / Q000737:chemistry; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution; D014556:Urine / Q000737:chemistry
chemical_list: D000470:Alkaloids; D004365:Drugs, Chinese Herbal; D007783:Lactones; C468415:neotuberostemonine
keywords: Excretion; Neotuberostemonine; Pharmacokinetics; Stemona tuberosa; Tissue distribution; UPLC-MS/MS