Electrospray Ionization Tandem Mass Spectrometry of the Two Main Antimalarial Drugs: Artemether and Lumefantrine

Ionizacao por electrospray no modo de ions positivos, e espectrometria de massas de alta resolucao e exatidao, e em tandem, realizadas em espectrometro de massas hibrido quadrupolo e tempo de voo, foram utilizadas para investigar a dissociacao quimica das moleculas intactas dos dois antimalaricos mais amplamente utilizados: artemeter e lumefantrina. As rotas de dissociacao das formas cationizadas e protonadas foram claramente estabelecidas via determinacoes de massas de alta resolucao e distribuicao isotopica. Os resultados obtidos podem auxiliar a monitorizacao e a quantificacao de artemeter e lumefantrina por LC-MS/MS, assim como de novos derivados ou outros farmacos antimalaricos estruturalmente relacionados. Electrospray ionization in the positive ion mode and high resolution and high accuracy tandem mass spectrometry performed in a hybrid quadrupole time-of-flight mass spectrometer were used to investigate the dissociation chemistry of the intact molecules of two most widely used antimalarial drugs: artemether and lumefantrine. The dissociation pathways of their cationized and protonated forms were rationalized based on high accuracy mass measurements and isotopic distributions. The obtained results should benefit LC-MS/MS monitoring and quantitation by mass spectrometry of the artemether and lumefantrine molecules, as well as of new derivatives or other structurally related antimalarial drugs.