Song Shuai, Tang Qingfa, Huo Huiling, Li Hancheng, Xing Xuefeng, Luo Jiabo
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.
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
J Anal Toxicol. 2015 Jan-Feb;39(1):58-68. doi: 10.1093/jat/bku113. Epub 2014 Oct 16.
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.
麻黄（中药名为麻黄）与附子（中药名为附子）的组合是中医的经典方剂，用于治疗感冒和风湿性关节痛。然而，由于含有麻黄碱和乌头生物碱的草药对心血管系统和中枢神经系统有潜在不良影响，因此受到严格监管。我们旨在研究麻黄 - 附子组合及单味草药提取物中11种生物碱在大鼠口服给药后的药代动力学。这些生物碱为去甲麻黄碱、去甲伪麻黄碱、麻黄碱、伪麻黄碱、甲基麻黄碱、乌头碱、中乌头碱、次乌头碱、苯甲酰乌头碱、苯甲酰中乌头碱和苯甲酰次乌头碱。采用简单、快速且灵敏的超高效液相色谱 - 串联质谱法，在14.5分钟内实现了包括两对非对映异构体在内的生物碱的同时测定。分离在Zorbax SB - Aq柱（100 mm×2.1 mm，3.5μm）上进行，流速为0.3 mL/min，以乙腈 - 0.1%甲酸水溶液为流动相。经验证的方法对复杂草药成分的定量分析显示出足够的灵敏度、选择性和分析效率。与单味草药提取物相比，血浆中的生物碱（甲基麻黄碱、苯甲酰中乌头碱和苯甲酰次乌头碱除外）消除较慢（平均驻留时间或半衰期较长），尽管血浆最大浓度和血浆浓度曲线下面积值降低。持续服药可能会发生蓄积。这些结果表明，药物监测对于麻黄 - 附子组合的安全使用可能至关重要。
