Determination of artemether and dihydroartemisinin in human plasma with a new hydrogen peroxide stabilization method. (June 2013)

• Record Type: Journal Article
• Authors: Huang, Liusheng; Olson, Alexander; Gingrich, David; Aweeka, Francesca T
• Is Part Of: Bioanalysis. Volume 5:Number 12(2013)
• Page Start: 1501
• Page End: 1506
• Publication Date: 2013-06
• Subjects: Drugs -- Analysis -- Periodicals; 615.19005
• DOI: 10.4155/bio.13.91
• Languages: English
• ISSNs: 1757-6180

Abstract

Background: Numerous methods have been reported for the determination of artemether (ARM) and its metabolite dihydroartemisinin (DHA) in plasma. However, stability issues in patient plasma have not received enough attention.Results: An LC–MS/MS method for simultaneous determination of ARM and DHA in human plasma (K3 EDTA) turned out to be problematic: ARM and DHA were degraded partially or completely in some patient plasma samples as indicated by the stable isotope-labeled internal standards. We postulated iron II (Fe 2+ ) in hemoglobin or its derived products from malaria patients causes degradation of the drugs, and found that hydrogen peroxide (H2 O2 ) protected the drugs from degradation. Acidifying plasma increased recovery of ARM significantly. Using only 50 µl of plasma sample, the method has a LLOQ at 0.5 ng/ml for both ARM and DHA.Conclusion: H2 O2 is a stabilizing agent for artemisinin derivatives. The modified method is reliable and sensitive.