Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Artemisinin Research Center, Beijing 100700, China.
Molecules. 2019 Jan 16;24(2):315. doi: 10.3390/molecules24020315.
Artemisinin (ART) is a highly effective antimalarial agent isolated from the traditional Chinese herb Qinghao. Metabolism of ART and its derivatives in the body is one of the most pressing issues for pharmaceutical scientists. Herein, an efficient in vitro microorganism model for simulation of metabolism of ART in vivo was developed employing Metabolites in the microbial transformation system and plasma of mice pre-administrated ART orally were analyzed by ultra-performance liquid chromatography (UPLC)-electrospray ionization (ESI)-quadrupole time-of-flight (Q-TOF)-mass spectrometry (MS) combined with UNIFI software. Thirty-two metabolites were identified in vitro and 23 were identified in vivo. After comparison, 16 products were found to be common to both models including monohydroxylated ART, dihydroxylated ART, deoxyartemisinin, hydroxylated deoxyartemisinin, hydroxylated dihydroartemisinin (DHA), and hydroxylated deoxy-DHA. These results revealed that CICC 40250 functioned as an appropriate model to mimic ART metabolism in vivo. Moreover, an overall description of metabolites of ART from CICC 40250 has been provided. Notably, DHA was detected and identified as a metabolite of ART in mouse plasma for the first time.
青蒿素（ART）是从传统中药青蒿中分离得到的一种高效抗疟药物。ART 及其衍生物在体内的代谢是药物科学家最关注的问题之一。在此，我们建立了一种高效的体外微生物模型，用于模拟 ART 在体内的代谢。采用超高效液相色谱（UPLC）-电喷雾电离（ESI）-四极杆飞行时间（Q-TOF）-质谱（MS）联用技术，结合 UNIFI 软件，分析了经口给予 ART 后的微生物转化体系和小鼠血浆中的代谢物。在体外鉴定了 32 种代谢物，在体内鉴定了 23 种代谢物。经比较，在两种模型中发现了 16 种共同的产物，包括单羟基化 ART、二羟基化 ART、去氧青蒿素、羟基化去氧青蒿素、羟基化二氢青蒿素（DHA）和羟基化去氧-DHA。这些结果表明 CICC 40250 可作为模拟 ART 体内代谢的合适模型。此外，还提供了 CICC 40250 中 ART 代谢物的全面描述。值得注意的是，首次在小鼠血浆中检测并鉴定出 DHA 是 ART 的代谢产物。
