Isoprene-derived oxygenated organic molecules (IP-OOM) drive new particle formation in the upper troposphere (Shen et al., 2024; Curtius et al., 2024), but the mechanisms that produce them, and the role of photochemistry in shaping their distribution, remain poorly constrained. These products are both hard to quantify, owing to isobaric and isotopic interferences that conventional time-of-flight mass spectrometers cannot resolve, and hard to interpret, as their formation pathways cannot be established from the measured product distribution alone. We address both with a combined measurement and modelling framework, which we demonstrate through chamber and flow reactor experiments. On the measurement side, we optimise a high-resolution Q Exactive Plus Orbitrap mass spectrometer, coupled to a bromide multi-scheme chemical ionisation inlet (the Br^–-MION2-Orbitrap), by tuning three operating parameters that change individual-species signals by 10–90 %. Benchmarked side by side against a Br^–-MION2-APi-TOF in chamber experiments, it agrees to within a factor of two for the oxygenated oxidation products while resolving isobaric interferences the time-of-flight instrument cannot. This comparison also shows that the Orbitrap’s apparent non-linearity at low concentrations, sometimes regarded as an intrinsic limitation, is rather an artefact of post-acquisition data processing: averaging that assigns zero intensity to non-detections biases the signal low near the detection limit. Disregarding the non-detections gives a conservative upper-bound detection limit of ∼1.3×10⁵ cm^−3, comparable to that of the APi-TOF. On the modelling side, we extend MARFORCE from simple inorganic chemistry to comprehensive organic mechanisms of hundreds of species coupled to transport, and add a continuous, spatially distributed OH source; the same model can also run as a well-mixed box model for chamber experiments. Applying the framework to the OH oxidation of 1,2–ISOPOOH in the flow reactor, we detect several abundant products absent from the current isoprene mechanism, and find that photolysis of the hydroperoxide-bearing products, a previously underappreciated process, shapes the product distribution. These experiments show how pairing molecular-level measurement with a model that resolves chemistry and transport provides a quantitative and transferable basis for studying the photochemical oxidation of isoprene and other volatile organic compounds relevant to upper-tropospheric aerosol formation.