Abstract: Mass spectrometry is widely recognized for its high sensitivity and rapid analysis capabilities, making it an indispensable tool in medical, environmental, and biological research. Pneumatic spray ionization (PSI), a unique ambient ionization technique requires no external electric field, effectively avoids redox side reactions and is therefore particularly suitable for in situ detection of redox-sensitive systems, such as battery electrolytes. Furthermore, the fine aerosol formed during the PSI process provides an ideal platform for microdroplet chemistry research. However, a major limitation of PSI is its inherently low ion yield, which places strict demands on the ion transmission efficiency of the atmospheric pressure interface (API) in mass spectrometers. To address this challenge, this work presented an orthogonal acceleration reflectron time-of-flight mass spectrometer (TOF MS) equipped with a variable-diameter radio-frequency octopole API, designed to overcome the low ion transmission efficiency and detection challenges under PSI conditions. The effects of radio frequency (1 MHz and 2 MHz) and peak-to-peak voltage (V_p-p) on the ion transmission efficiency of the octopole API were systematically investigated using a multi-component standard solution containing six compounds (m/z 39-606) and an electrospray ionization (ESI) source. The results showed that ion peak intensity increased firstly and then decreased with increasing V_p-p. When the radio frequency was 1 MHz, the maximum intensities for most ions occurred at a V_p-p of 40 V, except for the reserpine ion (m/z 609). In contrast, at 2 MHz, the mass discrimination effect was significantly reduced, enabling high transmission efficiency across a wider m/z range, especially in the low m/z region, such as for K⁺. Thus, a radio frequency of 2 MHz and a V_p-p of 100 V were chosen as optimized parameters. Under optimized conditions, the instrument demonstrated high sensitivity for the detection of reserpine, exhibiting good linearity within the range of 1-500 μg/L and achieving a limit of detection (LOD) of 0.3 μg/L. Compared with a linear ion trap, the present TOF MS showed superior resolution (up to 4 200 for m/z 195) and enabled accurate qualitative identification of low-mass ions, such as ambient ammonium ions, which are often challenging to resolve in lower-resolution instruments. Application validation confirmed that, when coupled with PSI, the system effectively detected ions across a broad mass range. The analysis of a caffeine solution revealed a series of protonated, sodiated, and multimeric cluster ions. More importantly, in the detection of vanadium (IV) electrolyte, various vanadyl-centered cluster ions were successfully captured without inducing changes in the valence state of vanadium. This confirms the method’s unique capability of avoiding redox side reactions and highlights its potential for in situ investigation of solvation structures in electrolyte systems.