4.1 Carbamazepine
Carbamazepine (CBZ), a drug used for treatment of epilepsy and neuropathic pain, is
one of the most thoroughly investigated substances regarding its uptake and
metabolization in plants [25]. The studies published so far were focusing on plants
with different intended usage. Those comprised edible plants such as cucumber [43],
tomato [37, 38], lettuce [37, 45, 47], spinach [47], arugula [47], radish [47], and
wheat [37], plants seen as potential candidates for phytotreatment (Typha spp.) [65],
a fungus (Pleurotus ostreatus) [73], and cell cultures from horseradish [57]. Thereby,
upon treatment with CBZ, apart from phase I metabolites formed by dehydration,
hydroxylation, and subsequent epoxidation, also several metabolites belonging to
phase II derived from conjugation of hydroxylated CBZ with amino acids and
hexoses were found. From the manifold studies on the interaction of plants with
CBZ, three stand out. One investigated synergistic effects when besides CBZ also
lamotrigine was taken up by the plant. In this case, a reduced formation of
dihydroxy-CBZ from the corresponding epoxide was observed due to inhibition of
epoxide hydrolase, a finding corresponding with results from human pharmacokinetic studies [43]. Due to the increased experimental effort, not too many studies use
plants cultivated in soil. Kodesova et al. investigated the uptake of CBZ (next to two
other common drugs) from eleven topsoils and two sub-soils (whereby drug stability
in the soil was also considered) [47].
The third study to be highlighted in this context investigated CBZ transformation
products in Armoracia rusticana cell culture. Thereby the effect of endophytic
rhizobacteria (Rhizobium radiobacter and Diaphorobacter nitroreducens) on the
formation of these metabolites was examined [57]. The results from this work
suggested that the reduction in CBZ concentrations could potentially be modulated
by the endophytic community. In a more fundamental way, this issue was already
researched in a study exploring the general potential of endophytic bacteria in
phytoremediation [74].
4.2 Non-steroidal Anti-inflammatory Drugs
With sales revenues exceeding 13 billion dollars alone in the United States,
non-steroidal anti-inflammatory drugs (NSAIDs) can be regarded as one of the
most prevalent drug classes for use in humans. As a negative side effect, traces of
NSAIDs are ubiquitous in the WWTP effluents and hence in the aquatic environment. This is also reflected in a particular scientific interest in the interaction of this
group of pharmaceuticals with plants. Thereby the majority of studies involved the
use of either diclofenac (DCF) [35, 40, 53, 58, 60, 75, 76] or ibuprofen (IBU)
[28, 69, 77–81], the two most prominent representatives within the group of
NSAIDs. To a lesser content, also naproxen [28, 35, 53], mefenamic acid [35, 53],
and KPF [35, 53] were investigated with respect to their interaction with plants such
Analytical Approaches for the Determination and Identification of Drug. . .
511
Carbamazepine (CBZ), a drug used for treatment of epilepsy and neuropathic pain, is
one of the most thoroughly investigated substances regarding its uptake and
metabolization in plants [25]. The studies published so far were focusing on plants
with different intended usage. Those comprised edible plants such as cucumber [43],
tomato [37, 38], lettuce [37, 45, 47], spinach [47], arugula [47], radish [47], and
wheat [37], plants seen as potential candidates for phytotreatment (Typha spp.) [65],
a fungus (Pleurotus ostreatus) [73], and cell cultures from horseradish [57]. Thereby,
upon treatment with CBZ, apart from phase I metabolites formed by dehydration,
hydroxylation, and subsequent epoxidation, also several metabolites belonging to
phase II derived from conjugation of hydroxylated CBZ with amino acids and
hexoses were found. From the manifold studies on the interaction of plants with
CBZ, three stand out. One investigated synergistic effects when besides CBZ also
lamotrigine was taken up by the plant. In this case, a reduced formation of
dihydroxy-CBZ from the corresponding epoxide was observed due to inhibition of
epoxide hydrolase, a finding corresponding with results from human pharmacokinetic studies [43]. Due to the increased experimental effort, not too many studies use
plants cultivated in soil. Kodesova et al. investigated the uptake of CBZ (next to two
other common drugs) from eleven topsoils and two sub-soils (whereby drug stability
in the soil was also considered) [47].
The third study to be highlighted in this context investigated CBZ transformation
products in Armoracia rusticana cell culture. Thereby the effect of endophytic
rhizobacteria (Rhizobium radiobacter and Diaphorobacter nitroreducens) on the
formation of these metabolites was examined [57]. The results from this work
suggested that the reduction in CBZ concentrations could potentially be modulated
by the endophytic community. In a more fundamental way, this issue was already
researched in a study exploring the general potential of endophytic bacteria in
phytoremediation [74].
4.2 Non-steroidal Anti-inflammatory Drugs
With sales revenues exceeding 13 billion dollars alone in the United States,
non-steroidal anti-inflammatory drugs (NSAIDs) can be regarded as one of the
most prevalent drug classes for use in humans. As a negative side effect, traces of
NSAIDs are ubiquitous in the WWTP effluents and hence in the aquatic environment. This is also reflected in a particular scientific interest in the interaction of this
group of pharmaceuticals with plants. Thereby the majority of studies involved the
use of either diclofenac (DCF) [35, 40, 53, 58, 60, 75, 76] or ibuprofen (IBU)
[28, 69, 77–81], the two most prominent representatives within the group of
NSAIDs. To a lesser content, also naproxen [28, 35, 53], mefenamic acid [35, 53],
and KPF [35, 53] were investigated with respect to their interaction with plants such
Analytical Approaches for the Determination and Identification of Drug. . .
511