Abstract
The (tentative) identification of unknown drug-related phase II metabolites in plants upon drug uptake remains a challenging task despite improved analytical instrument performance. To broaden the knowledge of possible drug metabolization, a fast-screening approach for the tentative identification of drug-related phase II metabolites is presented in this work. Therefore, an in silico database for the three non-steroidal anti-inflammatory drugs (ketoprofen, mefenamic acid, and naproxen) and a sub-group of their theoretical phase II metabolites (based on combinations with glucose, glucuronic acid, and malonic acid) was created. Next, the theoretical exact masses (protonated species and ammonia adducts) were calculated and used as precursor ions in an autoMS/MS measurement method. The applicability of this workflow was tested on the example of eleven edible plants, which were hydroponically grown in solutions containing the respective drug at a concentration level of 20 mg/L. For the three drugs investigated this led to the tentative identification of 41 metabolites (some of them so far not described in this context), such as combinations of hydroxylated mefenamic acid with up to four glucose units or hydroxylated mefenamic acid with two glucose and three malonic acid units.