Faculty of Chinese Medicine and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao 999078, PR China; Institute of International Standardization of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PR China.
Faculty of Chinese Medicine and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao 999078, PR China.
J Pharm Biomed Anal. 2022 Jan 20;208:114471. doi: 10.1016/j.jpba.2021.114471. Epub 2021 Nov 16.
Yunaconitine (YAC), crassicauline A (CCA), 8-deacetylyunaconitine (DYA), and 8-deacetylcrassicauline A (DCA), as hidden toxic Aconitum alkaloids, are detected in some products of processed Aconitum carmichaelii lateral root and poisoning cases. The distribution and toxicity of these four components in Aconitum herbs should be further systematically studied for medication safety. This study developed a new UHPLC-QQQ-MS/MS method to determine ten Aconitum alkaloids, including aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine, benzoylhypaconine, YAC, CCA, DYA, and DCA, for Aconitum herbs simultaneously. YAC and CCA were founded in some samples of unprocessed A. carmichaelii lateral root (7.04%), A. carmichaelii root (9.43%), A. brachypodum root (6.00%), and A. ouvrardianum root (100%). Four hidden toxic Aconitum alkaloids were detected in processed A. carmichaelii lateral root (2.56%) and A. vilmorinianum root (100%). Four hidden toxic Aconitum alkaloids played significant roles in the classification of Aconitum herbs by OPLS-DA analysis. The acute toxicity test was performed by up-and-down procedure (UDP). The oral administration of the half lethal dose (LD) of YAC, CCA, DYA, and DCA to female ICR mice was 2.37 mg/kg, 5.60 mg/kg, 60.0 mg/kg, and 753 mg/kg, respectively. The LD by intravenous injection was 0.200 mg/kg, 0.980 mg/kg, 7.60 mg/kg, and 34.0 mg/kg, respectively. The LD of unprocessed A. carmichaelii lateral root, A. vilmorinianum root, and A. brachypodum root to mice orally was 1.89 g/kg, 0.950 g/kg, and 0.380 g/kg, respectively. Symptoms of Aconitum alkaloid poisoning in mice were decreased activity, fur erect, palpebral edema, vomiting, polypnea, and convulsions. The main change of organs was flatulence. No poisoning or death occurred in mice at the maximum dosage (27.0 g/kg) of A. ouvrardianum root orally. To better control the quality and safety of Aconitum herbs, this study provides favorable support for improving the existing standards to strengthen the supervision of the four hidden toxic Aconitum alkaloids.
云乌头碱 (YAC)、粗茎乌头碱 A (CCA)、8-去乙酰基乌头碱 (DYA) 和 8-去乙酰基粗茎乌头碱 A (DCA) 作为隐藏的有毒乌头生物碱，在一些加工乌头侧根的产品和中毒病例中被检测到。为了用药安全，应对这些四种成分在乌头属植物中的分布和毒性进行进一步的系统研究。本研究开发了一种新的 UHPLC-QQQ-MS/MS 方法，用于同时测定十种乌头生物碱，包括乌头碱、次乌头碱、新乌头碱、苯甲酰乌头碱、苯甲酰次乌头碱、苯甲酰新乌头碱、YAC、CCA、DYA 和 DCA，用于乌头属植物。YAC 和 CCA 被发现在一些未经加工的乌头侧根 (7.04%)、乌头根 (9.43%)、短柄乌头根 (6.00%) 和乌头根 (100%) 中。在加工的乌头侧根 (2.56%) 和乌头根 (100%) 中检测到四种隐藏的有毒乌头生物碱。四种隐藏的有毒乌头生物碱在 OPLS-DA 分析中对乌头属植物的分类起到了重要作用。急性毒性试验采用上下法 (UDP) 进行。雌性 ICR 小鼠口服 YAC、CCA、DYA 和 DCA 的半致死剂量 (LD) 分别为 2.37mg/kg、5.60mg/kg、60.0mg/kg 和 753mg/kg，静脉注射 LD 分别为 0.200mg/kg、0.980mg/kg、7.60mg/kg 和 34.0mg/kg。未经加工的乌头侧根、乌头根和短柄乌头根对小鼠的口服 LD 分别为 1.89g/kg、0.950g/kg 和 0.380g/kg。乌头碱中毒小鼠的症状为活动减少、毛发竖起、眼睑水肿、呕吐、呼吸急促和抽搐。器官的主要变化是胀气。口服最大剂量 (27.0g/kg) 的乌头根未引起小鼠中毒或死亡。为了更好地控制乌头属植物的质量和安全性，本研究为改进现有标准提供了有利支持，以加强对这四种隐藏的有毒乌头生物碱的监管。
