Chemicals and reagents
Artesunate , dihydroartemisinin , pyronaridine , proguanil , clindamycin and trimipramine-d3 (I.S.) were sourced from Sigma-Aldrich (Steinheim, Germany). Cycloguanil was procured from Hycultec GmbH (Beutelsbach, Germany). Acetonitrile, methanol, 2-propanol, dimethyl sulfoxide (DMSO), ammonium formate, formic acid and drug free human serum were also procured from Sigma-Aldrich (Steinheim, Germany) and were LC–MS Grade. Blank Human EDTA-Plasma was obtained from the patients of the MultiMal Study at the Centre de Recherches Médicales de Lambaréné (CERMEL) (Lambaréné, Gabon) and the Kumasi Centre for Collaborative Research (KCCR) site at the St. Francis Xavier Hospital (Assin Foso, Ghana).
Equipment
The method was developed on a 1290 Infinity high performance liquid chromatography (HPLC) II…