Remote Infrared Matrix Assisted Laser Desorption Ionization (Remote IR MALDI) system (SpiderMass) with endogenous water as matrix allows to perform real-time DMPK in vivo. In this work, SpiderMass was used to analyze the impact on metabolite production or release of invalidated pro-protein PC1/3 macrophages by Short RNA (shRNA) versus scramble shRNA with Paclitaxel. Time course in vivo experiments were then performed on the inner and outer faces of patients' forearms or comedo treated with Melascreen (Ducray) containing ascorbyl glucoside. Finally, the impact of car pollution (emitted soot) on skin was also investigated. Taken together, we demonstrate that the SpiderMass instrument opens the door to clinical, pharmaceutical and environmental domains for real-time, in vivo pharmacokinetic (Drug Metabolism and PharmacoKinetics, DMPK) analysis.