High-performance liquid chromatography drift-tube ion-mobility quadrupole time-of-flight/mass spectrometry for the identity confirmation and characterization of metabolites from three statins (lipid-lowering drugs) in the model plant cress (Lepidium sativum) after uptake from water.

This work describes the metabolization of three different statins (lipid-lowering drugs) namely Atorvastatin, Fluvastatin and Simvastatin in the model plant cress (Lepidium sativum) after uptake from the growing medium. Analyzing plant extracts with HPLC hyphenated with a drift-tube ion-mobility quadrupole time-of-flight / mass spectrometer allowed the identity confirmation of more than 45 metabolites, resulting from oxidation/dehydrogenation, dehydration or hydroxylation of the parent drug or conjugation with amino acids and sugars. Metabolites were characterized by their retention times, m/z ratios, fragmentation patterns in MS/MS experiments, and their collision cross sections. Furthermore, a targeted analysis method for the trace-level analysis of the parent drugs as well as their metabolites in plant extracts was implemented by using HPLC coupled to triple quadrupole mass spectrometry in the multiple reaction monitoring mode. This approach was applied to study the metabolite distribution within the plant and to detect relative changes in metabolite concentrations as a function of growth time. Using a modified QuEChERS approach for extraction more than 50% of the metabolites could be still detected, if plants were exposed to only 1-10 µg L-1 of each statin.

Uptake and metabolism of the antidepressants sertraline, clomipramine, and trazodone in a garden cress (Lepidium sativum) model.

Environmental contamination with pharmaceuticals has received growing attention in recent years. Several studies describe the presence of traces of drugs in water bodies and soils and their impacts on nontarget organisms including plants. Due to these facts investigations of the uptake and metabolism of pharmaceuticals in organisms is an emerging research area. The present study demonstrates the analysis of three selected antidepressants (sertraline, clomipramine, and trazodone) as well as metabolites and transformation products in a cress model (Lepidium sativum). Cress was treated with tap water containing 10 mg/L of the parent drugs. Employing an analytical approach based on high performance liquid chromatography coupled with quadrupole time of flight or Orbitrap mass spectrometry in MS and MS² modes, in total 14 substances were identified in the cress extracts. All three parent drugs were taken up by the cress and translocated from the roots to the leaves in specific patterns. In addition to this, eleven metabolite species were identified. They were generated by hydroxylation, demethylation, conjugation with amino acids, or combinations of these mechanisms. Finally, the inclusion of control cultures in the experimental setup allowed for a differentiation of "true" metabolites generated by the cress and transformation products generated by plant-independent mechanisms.

Insights into the uptake, metabolization, and translocation of four non-steroidal anti-inflammatory drugs in cress (Lepidium sativum) by HPLC-MS2.

The metabolization of four non-steroidal anti-inflammatory drugs by cress (Lepidium sativum) was investigated using a HPLC-MS2 method. Cress was grown hydroponically in water containing 0.1 mg/L of each drug for investigations on the kinetics of drug uptake and metabolization over a growing period of 12 days. It could be shown that the parent drugs are metabolized and the abundance of both the parent drug and the metabolites formed, varies over time. Furthermore the distribution of the investigated substances within the different plant parts changed throughout the duration of the experiment due to translocation. Finally cress was cultivated in a solution containing the four drugs in concentrations as low as 0.001 mg/L to resemble the situation in real reclaimed wastewaters. Employing a QuEChERS approach for sample extraction and HPLC-MS2 in the multiple reaction monitoring mode allowed detecting nine metabolites in this cress sample.

High-performance liquid chromatography - mass spectrometry analysis of the parent drugs and their metabolites in extracts from cress (Lepidium sativum) grown hydroponically in water containing four non-steroidal anti-inflammatory drugs.

In this paper the metabolism of four non-steroidal anti-inflammatory drugs, (ketoprofen, mefenamic acid, naproxen, and diclofenac) by cress (Lepidium sativum) is described. Cress was cultivated hydroponically in water spiked with the parent drugs at levels ranging from 0.01mgL-1 to 1mgL-1. Employing an approach based on the analysis of the plant extracts by HPLC coupled either with quadrupole-time-of-flight mass spectrometry, or Orbitrap MS or triple quadrupole (QqQ) MS allowed the identification of twenty substances (sixteen metabolites and four parent drugs). Metabolites were formed from the parent drug by hydroxylation or conjugation with polar molecules such as glucose, small organic acids or amino acids. Introducing a pre-concentration step employing solid-phase extraction and using HPLC-QqQ/MS in the multiple reaction monitoring mode enabled the positive detection of 11 of the proposed metabolites next to the four parent components even in plants grown in a 0.01mgL-1 solution of the tested drugs, which is close to the conditions in real reclaimed waters.