Quantitative determination of artemisinin in rat hemolyzed plasma by an HPLC–HRMS method

Iron present in hemolyzed plasma could cause the degradation of artemisinin by reductively cleaving the peroxide bridge of artemisinin during sample preparation, which is a significant technical challenge for artemisinin determination. In this paper, this issue was resolved by using sodium nitrite as methemoglobin‐forming agent to oxidize hemoglobin to methemoglobin in the presence of acetic acid and prevent the degradation of artemisinin in hemolyzed plasma during the sample preparation procedure. Then, a high‐performance liquid chromatography tandem high‐resolution mass spectrometry method was developed and validated for the determination of artemisinin in normal and hemolyzed plasma. The linear range was validated over the concentration range of 5–500 ng ml −1 . The matrix effect and stability were also evaluated. This robust and sensitive assay was successfully applied to a pharmacokinetic study in rats after an oral administration of Artemisia annua L . extract.