High throughput quantitation of artesunate and its degradation products by flow injection gradient ratio standard addition mass spectrometry (FI-GRSA-MS)

Abstract

There is a pressing need to equip post-marketing drug quality surveillance systems with higher throughput and robust analytical tools that can reinforce pharmaceutical quality control to ensure safety of patients and integrity of treatment practices. This manuscript reports the development of a flow injection analysis mass spectrometry-based gradient ratio standard addition (FI-GRSA-MS) method for quantification of artesunate, a common antimalarial active pharmaceutical ingredient in a simple, efficient, accurate, and high throughput manner. Dodecylamine (DDA) was evaluated as an electrospray modifier for improving the sensitivity of the GRSA quantitation method. The linear dynamic range and precision for artesunate quantification were found to be 7 ng to 86 pg artesunate and 2.1%, respectively. When compared to high performance liquid chromatography, results were found to be equivalent at the 95% confidence level. To identify chemical markers of improper drug storage and artesunate degradation, tablets were artificially exposed to heat for time periods ranging between 1 and 12 hours and the degradation products detected were identified via accurate mass and isotopic cluster abundance measurements. Moreover, degradation behavior of artesunate tablets from two different manufacturers under identical degradation conditions was investigated, indicating that tablet formulation plays a significant role in the shelf life of these valuable medicines.