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.