Journal of Pharmaceutical and Biomedical Analysis ( IF 3.1 ) Pub Date : 2021-11-16 , DOI: 10.1016/j.jpba.2021.114471 Yu-Feng Huang 1 , Fan He 2 , Hao Cui 2 , Yan-Yu Zhang 2 , Hua-Yi Yang 2 , Zong-Suo Liang 3 , Wei Dai 4 , Chun-Song Cheng 2 , Ying Xie 5 , Liang Liu 5 , Zhong-Qiu Liu 6 , Hua Zhou 5
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 (LD50) 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 LD50 by intravenous injection was 0.200 mg/kg, 0.980 mg/kg, 7.60 mg/kg, and 34.0 mg/kg, respectively. The LD50 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.
中文翻译:
乌头常用药材中四种隐毒乌头生物碱的分布及其急性毒性的系统研究
乌头碱(YAC)、白头翁碱A(CCA)、8-脱乙酰乌头碱(DYA)和8-脱乙酰白头翁碱A(DCA)为隐性有毒乌头生物碱,在乌头侧根加工产品和中毒病例中检出。应进一步系统研究这四种成分在乌头药材中的分布和毒性,以确保用药安全。本研究开发了一种新的UHPLC-QQQ-MS / MS方法来确定10乌头类生物碱,包括乌头碱,中乌头碱,次乌头碱,苯甲酰,苯甲酰美沙乌头,benzoylhypaconine,YAC,CCA,DYA和DCA,为乌头同时草药。YAC 和 CCA 是在一些未加工的A. carmichaelii样品中建立的侧根 (7.04%)、A. carmichaelii根 (9.43%)、A. brachypodum根 (6.00%) 和A. ouvrardianum根 (100%)。在加工过的A. carmichaelii侧根 (2.56%) 和A. vilmorinianum根 (100%)中检测到四种隐藏的有毒乌头生物碱。通过OPLS-DA分析,四种隐藏的有毒乌头生物碱在乌头药材的分类中发挥了重要作用。急性毒性试验采用上下程序(UDP)进行。口服半致死剂量(LD 50) YAC、CCA、DYA 和 DCA 对雌性 ICR 小鼠的影响分别为 2.37 mg/kg、5.60 mg/kg、60.0 mg/kg 和 753 mg/kg。静脉注射的LD 50 分别为0.200mg/kg、0.980mg/kg、7.60mg/kg和34.0mg/kg。未加工的A. carmichaelii侧根、A. vilmorinianum根和A. brachypodum根对小鼠的口服LD 50分别为 1.89 g/kg、0.950 g/kg 和 0.380 g/kg。乌头生物碱中毒小鼠的症状为活动减少、毛皮直立、眼睑水肿、呕吐、呼吸急促和抽搐。器官的主要变化是胀气。A. ouvrardianum最大剂量(27.0 g/kg)小鼠未发生中毒或死亡根口。为更好地控制乌头药材的质量和安全,本研究为完善现有标准,加强对乌头四种隐性有毒生物碱的监管提供了有利的支持。