**5. Conclusions**

In this work, a rapid and sensitive method was developed to quantify the major flavonoids present in eleven *Ageratina havanensis* extracts obtained from two phenological states of *Ageratina havanensis*. The phenological state of the plant influences the concentration of sakuranetin, 7-methoxyaromadendrine and glycosides with *m*/*z* 447 in its extracts; in fact, the content of these compounds is higher in the vegetative state. In addition, the antioxidant potential of *Ageratina havanensis* (Kunth) R. M. King & H. Robinson extracts and its relationship with the concentration of major flavonoids were demonstrated for the first time. The results obtained in this study also highlight that this plant could be a source of new potential inhibitors of drug efflux mediated by P-gp. However, other in vitro and in vivo studies must be conducted to confirm the potential pharmacological or therapeutic relevance of these findings.

**Supplementary Materials:** The following are available online. Table S1: Equations for calibration curves, limit of detection (LDQ) and limit of quantitation (LOQ) by UPLC/ESI/TQD/MSn. Table S2: Summary of precision and accuracy results by UPLC/ESI/TQD/MSn, Table S3: Principal components selected for the PCA, Table S4: Most influential variables in PC. Figure S1: Chromatogram of sakuranetin at 25 μg/mL, Figure S2: Chromatogram of 7-methoxyaromadendrin at 25 μg/mL, Figure S3: MRM chromatogram of 7-methoxyaromadendrin and sakuranetin in the ethyl acetate extract of *Ageratina havanensis* leaves.

**Author Contributions:** Conceptualization, I.R., W.V., I.S. and L.R.; methodology, T.H.G., I.S. and L.R.; software, L.D.-R.; validation, I.S., C.Q.d.R., I.R. and M.T.P.L.; formal analysis, L.D.-R., Y.Á. and C.C.; investigation, T.H.G., C.Q.d.R., I.H.; resources, I.S. and L.R.; data curation, W.V.; writing—original draft preparation, T.H.G. and C.Q.d.R.; writing—review and editing, G.A. and L.R.; visualization, G.A. and L.R.; supervision, I.S. and L.R.; project administration, I.R., I.S. and L.R.; funding acquisition, I.S., L.D.-R., I.R., and M.T.P.L. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded by Project CAPES-MES "Sustainable use of Cuban and Brazilian biodiversity: Potentially bioactive: Natural Products from higher plants" (Process No. 122/11) and Visiting Research Program (PVE-Research Project, No. 400768/2014-3), CNPq, Brazil.

**Conflicts of Interest:** The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
