We have investigated the reactions of NO+, H3O+, O-2(+), and Kr+ with picric acid (2,4,6 trinitrophenol, C6H3N3O7, PiA) using a time-of-flight mass spectrometer with a switchable reagent ion source. NO+ forms a simple adduct ion PiA center dot NO+, while H3O+ reacts with PiA via nondissociative proton transfer to form PiAH(+). In contrast, both O-2(+) and Kr+ react with PiA by nondissociative charge transfer to produce Pig. For Kr+, we also observe dissociation of PiA, producing NO2+ with a branching percentage of approximately 40%. For the reagent ions H3O+ and O-2(+) (and operating the drift tube with normal laboratory air), we find that the intensities of the PiAH(+) and PiA(+) ions both exhibit a peak at a given drift-tube voltage (which is humidity dependent). This unusual behavior implies a peak in the detection sensitivity of PiA as a function of the drift-tube voltage (and hence E/N). Aided by electronic-structure calculations and our previous studies of trinitrotoluene and trinitrobenzene, we provide a possible explanation for the observed peak in the detection sensitivity of PiA.