Decoctions are a staple of traditional Chinese medicine. This study reports on a comprehensive analysis of the chemical compositions of both the supernatant and naturally-occurring precipitate of Sini decoction using ultra-high-performance liquid chromatography (UHPLC) hyphenated with quadrupole-Orbitrap high-resolution mass spectrometry (Q-Orbitrap HRMS). A total of 99 compounds (40 flavonoids, 34 alkaloids, 7 terpenoids, 3 phenolic acids and 15 other compounds) were tentatively identified in the full-scan MS/data-dependent MS/MS (full-scan MS1/dd-MS2) acquisition mode. Moreover, cold spray ionization-mass spectrometry (CSI-MS) was used to explore the presence of self-assembled complexes between phytochemical ingredients. As a proof-of-concept demonstration, the complexation between one acidic compound (glycyrrhizic acid) and three basic compounds (aconitine, hypaconitine, and mesaconitine) was characterized. This study may present inspiring scientific evidence for the formation of naturally-occurring precipitate, enabling a better understanding of Sini decoction and its therapeutic relevance. © 2021 Elsevier B.V.