Abstract: The primary ion guiding system is a crucial component of the ion optics system in a mass spectrometer, playing a pivotal role in the determining sensitivity of the instrument. The efficient transmission of ions with different mass-to-charge ratios (m/z) is influenced by multiple factors, including background gas pressure, flow velocity distribution, and the radiofrequency (RF) voltage amplitude applied to the quadrupole. Optimizing these parameters is essential for enhancing ion transmission efficiency and improving the overall performance of a mass spectrometer. Therefore, it is imperative to conduct a detailed study on the ion transmission process within the primary ion guiding system under multi-physics coupling conditions, while also validate and optimize simulation models using experimental data. In this study, a fluid simulation model of the primary ion guiding system was constructed based on computational fluid dynamics (CFD) using specialized fluid simulation software. This model was employed to analyze the pressure and flow velocity distribution of the background gas under ideal conditions. Then, the simulated fluid field data, serving as background gas parameters, was imported into the ion optics simulation software (SIMION). Subsequently, the motion trajectories of ions with different m/z ratios were analyzed at different RF voltage amplitudes to assess their transmission characteristics. The simulation results indicated that when the RF voltage amplitude of the quadrupole is within the range of 0-133.6 V, the transmission efficiency of ions with different m/z ratios initially increases as the RF voltage rises, reaches the maximum transmission efficiency, and then gradually decreases. Furthermore, as the m/z ratio increases, the RF voltage required to achieve the peak transmission efficiency also increases. Additionally, when the background gas pressure increases, the ion transmission bandwidth expands, suggesting that gas pressure is a critical factor in controlling ion transportion properties. To validate these findings, experimental verification was conducted, the ion transportation efficiency of different m/z ratios under varying RF voltage amplitudes was compared with the simulation results. The experimental data exhibit strong agreement with the simulations, confirming the accuracy and reliability of the developed model. This study provides both theoretical foundations and experimental support for the optimized design of the primary ion guiding system in a mass spectrometer.