Panzerina lanata is a Chinese medicine with the bioactivity of detumescence and detoxification. In this study, novel qualitative and quantitative methods were established by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry and ultra-high-performance liquid chromatography-triple quadrupole linear ion trap mass spectrometry, respectively. As a result, 20 compounds were identified or tentatively characterized including flavonoids, organic acids, alkaloids, and lignans, five of which were identified for the first time based on the reference standards. The quantitative approach exhibited good linearity (R-2 > 0.995), precision (RSDs < 4.97%), stability (RSDs < 4.77%), and recovery (96.04-104.14%). Afterward, this method was implemented to determine 11 flavonoids in four batches of P. lanata. Among them, seven compounds were quantified for the first time. Narcissin was abundant in each batch of P. lanata (average of 10.890-14.230 mg/g) with the highest quantities. The results provide valuable information for quality evaluation.