title: Ultra-performance liquid-chromatography with tandem mass spectrometry performing pharmacokinetic and biodistribution studies of croomine, neotuberostemonine and tuberostemonine alkaloids absorbed in the rat plasma after oral administration of Stemonae Radix.
abstract: Stemonae Radix (Stemona tuberosa Lour, Bai Bu) is an important traditional Chinese medicinal (TCM) plant known for its antitussive activity. Croomine, neotuberostemonine and tuberostemonine alkaloids of Stemonae Radix are major components responsible for antitussive action. In this work, plasma pharmacokinetic and biodistribution characteristics of the three alkaloids after oral administration of Stemonae Radix are investigated using a rapid and sensitive UPLC-Q-TOF-HDMS method. Mass spectrometry (MS) was performed on a Waters Micromass high-definition technology with an electrospray ionization source in positive ion mode, with excellent MS mass accuracy and enhanced MS data acquisition. Separation of main alkaloids was achieved on a Waters BEH C(18) column by linear gradient elution. Data were analyzed and estimated by compartmental methods and pharmacokinetic parameters calculated using WinNonlin Professional version 5.1. It was found that croomine, neotuberostemonine and tuberostemonine had faster absorbed into the bloodstream, maintain the high plasma concentration, and pose a large AUC value. The biodistribution of neotuberostemonine and tuberostemonine showed that the higher levels were in liver, and lung. Croomine was discovered in brain and showed that it could cross the blood-brain barrier, indicating that croomine plays an antitussive effect as acting on the central nervous system. Neotuberostemonine and tuberostemonine were not discovered in brain, demonstrating that they play an antitussive effect as peripheral antitussive. This work suggests that the pharmacokinetics and biodistribution based-UPLC-Q-TOF-HDMS can provide a reliable tools for screening bioactive components contributing to pharmacological effects of medicinal herbs.
authors.affiliation: National TCM Key Lab of Serum Pharmacochemistry, Heilongjiang University of Chinese Medicine, and Key Pharmacometabolomics Platform of Chinese Medicines, Heping Road 24, Harbin 150040, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.forename: Wei
authors.initials: W
authors.lastname: Dong
authors.forename: Aihua
authors.initials: A
authors.lastname: Zhang
authors.forename: Weiming
authors.initials: W
authors.lastname: Wang
authors.forename: Xijun
authors.initials: X
authors.lastname: Wang
mesh_terms: D000284:Administration, Oral; D000470:Alkaloids / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D002853:Chromatography, Liquid / Q000379:methods*; D006207:Half-Life; D007783:Lactones / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D008516:Medicine, Chinese Traditional; D015394:Molecular Structure; D018517:Plant Roots / Q000737:chemistry; D011759:Pyrrolidines / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D013141:Spiro Compounds / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D041901:Stemonaceae / Q000737:chemistry*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014018:Tissue Distribution
chemical_list: D000470:Alkaloids; D007783:Lactones; D011759:Pyrrolidines; D013141:Spiro Compounds; C468415:neotuberostemonine; C034243:tuberostemonine; C082845:croomine