Determination of podophyllotoxin and related aryltetralin lignans by HPLC/DAD/MS from Lamiaceae species

Leaves of different species of Lamiaceae (Hyptidinae) have been shown to contain podophyllotoxin, a lignan generally extracted from the roots and rhizomes of Podophyllum species. This compound is important because its semi-synthetic derivatives (etoposide, teniposide and etopophos) are used in cancer treatment. This work describes the development of an analytical methodology to recognize genera/species of Hyptidinae as alternative sources of podophyllotoxin through the identification and quantification of podophyllotoxin, yatein, α-peltatin and β-peltatin in semi-purified extracts of Brazilian species. The quantifications were performed in enriched extracts analyzed in a RP18 endcapped column using the A phase (MeOH: H2O: MeCO2H 14:85:1) and B phase (acetonitrile) as mobile phases at a flow rate of 0.8 mL/min, diode array detection, and mass spectrometry with positive ESI. The lignan profiles present in the species were interpreted using PCA and HCA analysis. The method was demonstrated to be linear, precise, accurate and specific. The greatest lignan content was detected in the aerial parts of Leptohyptis calida, including 1.57% podophyllotoxin in the leaves and 0.21% in the flowers and 1.94% of α-peltatin in the leaves and 0.52% in the flowers as measured by dry weight of plant material. So, this work demonstrated that several genera within Hyptidinae may potentially serve as an alternative source of podophyllotoxin, and, the extraction procedure as well as the exploratory study of lignans using multivariate methods (PCA and dendrogram) revealed an intrinsic relationship between podophyllotoxin and α-peltatin levels in different part of the plant.