Dereplication of podophyllotoxin and related cytotoxic lignans in Hyptis verticillata by ultra‐high‐performance liquid chromatography tandem mass spectrometry

Abstract

Introduction Hyptis verticillata Jacq. (Lamiaceae) is a Mexican medicinal plant for the treatment of skin infections and illness affecting the respiratory and gastrointestinal systems. Objective To associate the efficient resolution provided by ultra‐high‐performance liquid chromatography combined to the accuracy of a hybrid Fourier‐transform (FT) mass spectrometer in order to dereplicate podophyllotoxin‐type lignans in a plant extract. Methods An ultra‐high‐performance liquid chromatography‐photodiode array‐high resolution electrospray ionisation tandem mass spectrometry (UHPLC‐PDA‐HRESI‐MS/MS) method was applied in an Orbitrap hybrid FT spectrometer for dereplication of podophyllotoxin and related cytotoxic lignans in wild bushmint. This procedure included high‐resolution mass values for positively charged ions [M + H]+ and [M + NH4]+, MS/MS data, and comparison of UV maxima and retention times with pure compounds. Results Podophyllotoxin in addition to seven aryltetralins, four arylnaphthalenes, and one dibenzylbutyrolactone were dereplicated from the methanol extract in a short‐time analysis (5 min). 4′‐O‐Demethyl‐dehydro‐deoxypodophyllotoxin was identified as a new natural product. Conclusion The applied UHPLC‐MS/MS dereplication method is suitable for a rapid analysis of podophyllotoxin‐type lignans and the resulting chemical fingerprinting could be valuable in quality control of herbal drugs and their phytopharmaceuticals.

Subtribe Hyptidinae (Lamiaceae): A promising source of bioactive metabolites

“…Further studies with the same plant afforded podophyllotoxin ( 124 ), hyptinin ( 125 ), podorhizol ( 126 ), epipodorhizol ( 127 ) ( Kuhnt et al, 1994 ), hyptoside ( 128 ) and deoxypicropodophyllin ( 129 ) ( Hamada et al, 2012 ). More recently, β -peltatin-6- O -glucoside ( 130 ), 4ʹ-demethyl-deoxypodophyllotoxin-4ʹ- O -glucoside ( 131 ), 4′- O -demethyldehydrodeoxy podophyllotoxin ( 132 ) and deoxypodophyllotoxin ( 133 ), besides the previously reported lignans 114 , 115 , 118 , 119 , 120 , 123 , 124 were isolated from the species ( Fragoso-Serrano and Pereda-Miranda, 2020 ).

Fig.

…”

“…Moreover, recently, an ultra - high - performance liquid chromatography - photodiode array - high resolution electrospray ionization tandem mass spectrometry (UHPLC - PDA - HRESI - MS/MS) method, aiming at to dereplicate podophyllotoxin-type lignans in Condea verticillata (syn. Hyptis verticillata ) has also been proposed ( Fragoso-Serrano and Pereda-Miranda, 2020 ). Besides that, efforts to obtain podophyllotoxin from tissue culture of Hyptidinae species have been successfully carried out.…”