Rapid On-Site Detection of Ginsenosides in Panax ginseng Using Portable Miniature Mass Spectrometry by Sodium Acetate-Enhanced Nanoelectrospray Ionization and a Same-Spectrum Same-Screening Quantification Strategy

Abstract Ginsenosides are the major bioactive constituents in Panax ginseng (PG), exhibiting diverse pharmacological effects, including anticancer, neuroprotective, cardioprotective, and anti-inflammatory activities. On-site mass spectrometry (MS) analysis of ginsenosides plays a crucial role in PG quality control. However, owing to matrix effects, structural complexity, low volatility, poor proton affinity, and the presence of multiple glycosidic moieties, rapid analysis of ginsenosides using portable MS under ambient conditions remains challenging. Here, we developed a sodium acetate (NaOAc)-enhanced nanoelectrospray ionization (nESI) method enabling rapid, on-site ginsenoside profiling using miniature mass spectrometry (mMS). NaOAc-mediated cationization promotes efficient formation of [M + Na]+ ions, enhancing ion signal intensity. Ginsenosides were detected using full-scan MS and MS/MS, including Rb1, Rg1, Re, Rd, Rf, notoginsenoside R1, etc. For quantitative analysis of the three pharmacopoeial markers (Rb1, Rg1, and Re), a same-spectrum and same-screening (4S) strategy using structurally similar saponins as an internal standard was established. The method exhibited good linearity (5–100 μg·mL–1, R2 > 0.99), acceptable precision (RSD < 13%), and recoveries. The limits of detection (LOD) for Rb1, Rg1, and Re were 0.10–0.20 μg·mL–1, respectively. Application of the method to PG samples of different cultivation ages revealed that the Rb1/Re ratio strongly correlated with cultivation age. This work demonstrated a practical strategy to enhance ionization efficiency and quantitative robustness in mMS and provided a feasible approach for on-site chemical assessment of herb medicines.