title: Simultaneous quantification and pharmacokinetics of alkaloids in Herba Ephedrae-Radix Aconiti Lateralis extracts.
abstract: The combination of Herba Ephedrae (Mahuang in Chinese) and Radix Aconiti Lateralis (Fuzi in Chinese) is a classical preparation in traditional Chinese medicine and used for treating colds and rheumatic arthralgia. However, herbal medicines containing ephedrines and Aconitum alkaloids are strictly regulated because of the potential for adverse effects on the cardiovascular system and the central nervous system. We aimed to investigate the pharmacokinetics of 11 alkaloids in the Mahuang-Fuzi combination and single-herb extracts after oral administration in rats. The alkaloids were norephedrine, norpseudoephedrine, ephedrine, pseudoephedrine, methylephedrine, aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine and benzoylhypaconine. Simultaneous determination of the alkaloids, including two pairs of diastereomers, was achieved in 14.5 min by a simple, rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry method. The separation was performed on a Zorbax SB-Aq column (100 mm × 2.1 mm, 3.5 μm) at a flow rate of 0.3 mL/min using acetonitrile-0.1% formic acid aqueous solution as the mobile phase. The validated method demonstrated adequate sensitivity, selectivity and process efficiency for the quantitative analysis of complex herbal components. Compared with single-herb extracts, alkaloids in plasma (except methylephedrine, benzoylmesaconine and benzoylhypaconine) showed slower elimination (the mean residence time or half-life was longer), although the maximum plasma concentration and area under the plasma concentration curve values decreased. Accumulation may occur with continuous drug intake. These results suggest that drug monitoring may be essential for the safe use of the Mahuang-Fuzi combination.
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou 510515, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Song
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou 510515, China.
authors.forename: Qingfa
authors.initials: Q
authors.lastname: Tang
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou 510515, China.
authors.forename: Huiling
authors.initials: H
authors.lastname: Huo
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou 510515, China.
authors.forename: Hancheng
authors.initials: H
authors.lastname: Li
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou 510515, China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Xing
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou 510515, China ljb@smu.edu.cn.
authors.forename: Jiabo
authors.initials: J
authors.lastname: Luo
mesh_terms: D000157:Aconitine / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics; D031841:Aconitum / Q000737:chemistry*; D000284:Administration, Oral; D000470:Alkaloids / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D002853:Chromatography, Liquid; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000493:pharmacokinetics*; D004809:Ephedrine / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics; D006207:Half-Life; D057230:Limit of Detection; D008297:Male; D010665:Phenylpropanolamine / Q000097:blood / Q000493:pharmacokinetics; D010936:Plant Extracts / Q000737:chemistry / Q000493:pharmacokinetics*; D054199:Pseudoephedrine / Q000097:blood / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry
chemical_list: D000470:Alkaloids; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; C479202:benzoylhypaconine; C005331:norpseudoephedrine; D010665:Phenylpropanolamine; C047307:benzoylaconine; C058309:hypaconitine; C041707:N-methylephedrine; C019470:mesaconitine; D054199:Pseudoephedrine; D004809:Ephedrine; C085283:benzoylmesaconine; D000157:Aconitine