4.4 Other Drugs for Use in Humans
One of the more early examples for research focused on the formation of drug
metabolites in plants after treatment with the parent drug (here PAR) is the detection
of PAR-glutathione, PAR-cysteine, and PAR-glucose in Armoracia rusticana cell
culture reported by Huber et al. [36]. In this work, the cell culture was incubated with
an exceptionally high concentration of PAR (~160 mg L
À1 ), and extracts from the
harvested cells were subsequently analyzed by HPLC coupled to a low-resolution
mass spectrometer (ion trap). MS
2 experiments were used to acquire knowledge on
the metabolite structures. To further support data from HPLC-MS analysis, enzymatic hydrolysis was performed revealing the cleavage of glucose from the
PAR-glucoside. A further study on PAR metabolism by cucumber was published
10 years later by Sun et al. [41].
A major problem encountered in many of the studies devoted to identifying the
metabolites formed in plants upon uptake of PPCPs is the lack of suitable standards,
particularly when it comes to phase II metabolites. For this reason as much information as possible about the compounds detected should be gathered. Investigating
the interaction of garden cress with three statins, Emhofer et al. introduced DT-IM
QTOF/MS offering a further parameter (collision cross sections) for compound
characterization [54]. Stable isotope labeling-assisted metabolite probing for the
detection of metabolites formed within the plant was tested on the example of
Arabidopsis thaliana treated with gemfibrozil [63]. The unique diagnostic pattern
due to the use of 1:3 mixture of deuterated and non-deuterated gemfibrozil facilitated
the spotting of 11 novel phase II drug-conjugates in plant extracts [63]. The
workflow employed in that study is depicted in Fig. 4.
MS imaging (MSI) may be used to illustrate the tissue distribution of drugs as
well as their metabolites with a plant. Vilette et al. presented an MSI approach for
elucidating the spatial distribution of telmisartan and its metabolites (among other
drugs) in Salix alba leaves [67]. A multi-analyte approach was chosen by Hurtado
et al. when analyzing lettuce grown in the presence of a series of different contaminants [44]. Their approach involved the use of ß-glucosidase to cleave off glucose
moieties from phase II metabolites derived from a variety of parent drugs and PCPs.
Comparing the results from extracts treated with ß-glucosidase and untreated ones
allowed to judge the degree of metabolization. Information about further studies on
interactions of plants with caffeine [46], benzodiazepines [59], antidepressants [55],
steroid estrogens [49], and metformin [84] may be extracted from Table 1.
The X-ray contrast agent iopromide was tested with Typha latifolia whereby a
large number of mainly phase I metabolites were detected [85].
514
F. Mlynek et al.
One of the more early examples for research focused on the formation of drug
metabolites in plants after treatment with the parent drug (here PAR) is the detection
of PAR-glutathione, PAR-cysteine, and PAR-glucose in Armoracia rusticana cell
culture reported by Huber et al. [36]. In this work, the cell culture was incubated with
an exceptionally high concentration of PAR (~160 mg L
À1 ), and extracts from the
harvested cells were subsequently analyzed by HPLC coupled to a low-resolution
mass spectrometer (ion trap). MS
2 experiments were used to acquire knowledge on
the metabolite structures. To further support data from HPLC-MS analysis, enzymatic hydrolysis was performed revealing the cleavage of glucose from the
PAR-glucoside. A further study on PAR metabolism by cucumber was published
10 years later by Sun et al. [41].
A major problem encountered in many of the studies devoted to identifying the
metabolites formed in plants upon uptake of PPCPs is the lack of suitable standards,
particularly when it comes to phase II metabolites. For this reason as much information as possible about the compounds detected should be gathered. Investigating
the interaction of garden cress with three statins, Emhofer et al. introduced DT-IM
QTOF/MS offering a further parameter (collision cross sections) for compound
characterization [54]. Stable isotope labeling-assisted metabolite probing for the
detection of metabolites formed within the plant was tested on the example of
Arabidopsis thaliana treated with gemfibrozil [63]. The unique diagnostic pattern
due to the use of 1:3 mixture of deuterated and non-deuterated gemfibrozil facilitated
the spotting of 11 novel phase II drug-conjugates in plant extracts [63]. The
workflow employed in that study is depicted in Fig. 4.
MS imaging (MSI) may be used to illustrate the tissue distribution of drugs as
well as their metabolites with a plant. Vilette et al. presented an MSI approach for
elucidating the spatial distribution of telmisartan and its metabolites (among other
drugs) in Salix alba leaves [67]. A multi-analyte approach was chosen by Hurtado
et al. when analyzing lettuce grown in the presence of a series of different contaminants [44]. Their approach involved the use of ß-glucosidase to cleave off glucose
moieties from phase II metabolites derived from a variety of parent drugs and PCPs.
Comparing the results from extracts treated with ß-glucosidase and untreated ones
allowed to judge the degree of metabolization. Information about further studies on
interactions of plants with caffeine [46], benzodiazepines [59], antidepressants [55],
steroid estrogens [49], and metformin [84] may be extracted from Table 1.
The X-ray contrast agent iopromide was tested with Typha latifolia whereby a
large number of mainly phase I metabolites were detected [85].
514
F. Mlynek et al.