School of Pharmaceutical Sciences, Shandong University, Jinan, P. R. China.
J Sep Sci. 2019 Nov;42(21):3330-3339. doi: 10.1002/jssc.201900668. Epub 2019 Sep 18.
The traditional antimalarial herb Artemisia annua L., from which artemisinin is isolated, is widely used in endemic regions. It has been suggested that artemisinin activity can be enhanced by flavonoids in A. annua; however, how fast and how long the flavonoids are present in the body remains unknown. In the present study, a rapid and sensitive liquid chromatography with tandem mass spectrometry method was developed and validated for the simultaneous determination of three major flavonoids components, i.e. chrysosplenol D, chrysoplenetin, and artemetin and their glucuronidated metabolites in rats after oral administrations of A. annua extracts at a therapeutic ultra-low dose. The concentration of the intact form was determined directly, and the concentration of the glucuronidated form was assayed in the form of flavonoids aglycones, after treatment with β-glucuronidase/sulfatase. The method was linear in the range of 0.5-300.0 ng/mL for chrysoplenetin and artemetin, and 2-600 ng/mL for chrysosplenol D. All the validation data conformed to the acceptance requirements. The study revealed a significantly higher exposure of the flavonoid constituents in conjugated forms in rats, with only trace intact from. Multiple oral doses of A. annua extracts led to a decreased plasma concentration levels for three flavonoids.
传统的抗疟草药黄花蒿（Artemisia annua L.），从中分离出青蒿素，在流行地区被广泛使用。有人提出，青蒿素的活性可以通过黄花蒿中的类黄酮增强；然而，类黄酮在体内存在的速度和时间长短仍不清楚。在本研究中，开发并验证了一种灵敏的液相色谱-串联质谱法，用于同时测定大鼠口服黄花蒿提取物治疗超低剂量后三种主要黄酮类成分，即 chrysosplenol D、chrysoplenetin 和 artemetin 及其葡萄糖醛酸代谢物。直接测定完整形式的浓度，并用β-葡萄糖醛酸酶/硫酸酯酶处理后，以黄酮苷元的形式测定葡萄糖醛酸结合形式的浓度。该方法对 chrysoplenetin 和 artemetin 的线性范围为 0.5-300.0ng/mL，对 chrysosplenol D 的线性范围为 2-600ng/mL。所有验证数据均符合验收要求。研究表明，在大鼠中，结合形式的黄酮类成分的暴露量明显更高，只有痕量的完整形式。多次口服黄花蒿提取物后，三种黄酮类化合物的血浆浓度水平降低。
