In this study, we developed a method using UPLC-ESI-MS/MS to simultaneously determine the contents of forsythoside B, loganin, macranthoidin B, dipsacoside B, rutin, arctiin, phillyrin, pinoresinol-β-D-glucoside, 3,5-dicaffeoylquinic acid, 3,4-dicaffeoylquinic acid, isoquercitrin, hyperoside, astragalin, luteoloside, genistin, arctigenin, neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, quercetin, luteolin, genistein, quinic acid, caffeic acid, isoforsythoside and forsythoside A in Flos Lonicerae japonicae–Fructus Forsythiae herb couple with a run time of only 8 min. The separation was performed on an Acquity UPLC HSS T3 C18 column (100 mm × 2.1 mm, 1.8 μm) at a flow rate of 0.4 mL min−1, and acetonitrile/methanol (4 : 1, v/v) – 0.4% formic acid was used as the mobile phase. Variations in the intra- and inter-day precision of all analytes were below 5.00%; the matrix effect of all the analytes was found to be within the acceptable range; and the accuracy was evaluated by a recovery test within the range of 95.63–103.10%. The method successfully quantified the twenty-six compounds in the Flos Lonicerae japonicae–Fructus Forsythiae herb couple. Moreover, it transpired through hierarchical cluster analysis and principal component analysis that the consistency of the Flos Lonicerae japonicae–Fructus Forsythiae herb couple as the two important herbs in Flos Lonicerae japonicae–Fructus Forsythiae herb couple preparations (Shuang-Huang-Lian oral liquid, Yin-Qiao-Jie-Du tablet and Fufang Qin-Lan oral liquid), except that in Qin-Re-Jie-Du oral liquid was relatively good. The results showed that the method was accurate, sensitive and reliable.
