This study addresses the important question of how mammalian inositol pyrophosphates PP-InsP levels are changing in response to reactive oxygen species (ROS). Using capillary electrophoresis electrospray ionization mass spectrometry (summarized MS data presented in dataset files), the authors found that the application of β-lapachone, a quinone drug that generates oxidative stress in cellulo, reduces PP-InsP levels. The inhibition was dependent on the presence of NQO1 (Western blots) and was achieved at least partially by inhibiting IP6K (PAGE gels). This study thus provides mechanistic insights into the pharmacology of β-lapachone.