Aconitum carmichaelii Debeaux is a widely used herbal medicine, which has anti-inflammatory and analgesic activities. However, due to its high toxicity, poisoning incidents often occur all over the world. To systematically understand the pharmacokinetics (PK) and tissue distribution of A. carmichaelii, 18 representative alkaloids, including 8 amine- (ADA), 4 monoester- (MDA) and 6 diester-type (DDA) diterpenoid alkaloids, were simultaneously quantified by ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC-QQQ-MS) with dynamic multiple reaction monitoring (MRM) mode. PK results suggested that benzoylmesaconine, mesaconitine, 10-OH-aconitine and aconitine had lower bioavailability, which might relate to the substitution at C-3. In tissue distribution, alkaloids present higher concentrations in the liver, kidney, and only songorine, neoline and benzoyldeoxyaconine were detected in the brain. Moreover, the concentrations of extremely toxic DDAs in high-dose group were much higher than that of low-dose group, indicating that these DDAs might be the main reason for the toxicity of Aconitum. The results also suggested that benzoyldeoxyaconine and deoxyaconitine should be determined for the quality control of A. carmichaelii due to their high concentrations in both herbal extract and tissues. The systematic investigation into these 18 representative alkaloids could basically illuminate the PK and distribution of A. carmichaelii in rats, and provide some information for clinical studies.

中文翻译：

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UHPLC-QQQ-MS鉴定鼠头乌头十八种主要生物碱的药代动力学和组织分布。

乌头乌头是一种广泛使用的草药，具有抗炎和镇痛作用。但是，由于其高毒性，世界各地经常发生中毒事件。为了系统地了解卡氏假单胞菌的药代动力学（PK）和组织分布，同时通过超定量法同时定量了18种代表性生物碱，包括8种胺（ADA），4种单酯（MDA）和6种二酯型（DDA）二萜类生物碱。动态多反应监测（MRM）模式的高效液相色谱-三重四极杆质谱（UHPLC-QQQ-MS）。PK结果表明，苯甲酰基美沙可碱，间皮肉碱，10-OH-aco肉碱和乌头碱具有较低的生物利用度，这可能与C-3的取代有关。在组织分布中，生物碱在肝脏，肾脏，大脑中仅检测到松香碱，新碱和苯甲酰脱氧乌头碱。此外，高剂量组的剧毒DDAs浓度远高于低剂量组，说明这些DDAs可能是乌头中毒的主要原因。结果还表明，应确定苯甲酰脱氧乌头碱和脱氧可卡因碱，因为它们在草药提取物和组织中的浓度都很高，因此可以用于卡氏假单胞菌的质量控制。对这18种代表性生物碱的系统研究可以从根本上阐明大鼠拟南芥的PK和分布，并为临床研究提供一些信息。高剂量组的高毒性DDAs浓度远高于低剂量组，说明这些DDAs可能是乌头中毒的主要原因。结果还表明，应确定苯甲酰脱氧乌头碱和脱氧可卡因碱，因为它们在草药提取物和组织中的浓度都很高，因此可以用于卡氏假单胞菌的质量控制。对这18种代表性生物碱的系统研究可以从根本上阐明大鼠拟南芥的PK和分布，并为临床研究提供一些信息。高剂量组的高毒性DDAs浓度远高于低剂量组，说明这些DDAs可能是乌头中毒的主要原因。结果还表明，应确定苯甲酰脱氧乌头碱和脱氧可卡因碱，因为它们在草药提取物和组织中的浓度都很高，因此可以用于卡氏假单胞菌的质量控制。对这18种代表性生物碱的系统研究可以从根本上阐明大鼠拟南芥的PK和分布，并为临床研究提供一些信息。Carmichaelii，因为它们在草药提取物和组织中的浓度很高。对这18种代表性生物碱的系统研究可以基本阐明大鼠拟南芥的PK和分布，并为临床研究提供一些信息。Carmichaelii，因为它们在草药提取物和组织中的浓度很高。对这18种代表性生物碱的系统研究可以从根本上阐明大鼠拟南芥的PK和分布，并为临床研究提供一些信息。