Degradation and ecotoxicity of the biomedical drug artemisinin in soil

Abstract

The plant Artemisia annua L. is cropped in many countries for production of the antimalarial drug artemisinin. Artemisinin is phytotoxic and has insecticidal activity. Large-scale cultivation of A. annua may cause transfer of artemisinin to soil and, hence, may affect both soil organisms and the aquatic environment if the compound is leachable. In the present study, a new method for extraction of artemisinin from soil was developed, and field concentrations and degradation kinetics of artemisinin in sandy and loamy soils were measured. The soil concentrations in a Danish A. annua field were up to 11.7 mg/kg. The degradation kinetics could be modeled as the sum of two first-order reactions, a fast initial degradation followed by a reaction that was 11- to 25-fold slower. It took at least 35 d before artemisinin could not be detected (<0.36 mg/kg) at 20 degrees C, classifying artemisinin as being relatively persistent in the environment. Combined with its water solubility of 49.7 +/- 3.7 mg/L, this makes it potentially leachable. In soil, artemisinin repelled the earthworm (Eisenia fetida; the 10 and 50% effect concentrations [EC10s and EC50s, respectively] were 5.24 +/- 2.64 and 21.57 +/- 4.73 mg/kg, respectively) and inhibited growth of lettuce (Lactuca sativa L.; EC50, 2.48 mg/kg). Springtails (Folsomia candida) were not affected in the tested concentration range of 1 to 100 mg/kg. Artemisinin had toxicity to the freshwater algae (Pseudokirchneriella subcapitata; EC50, 0.24 +/- 0.01 mg/L) and duckweed (Lemna minor; EC50, 0.19 +/- 0.03 mg/L) similar to that of the commercial herbicide atrazine. Based on the presented data, the risks of adverse environmental effects because of cultivation of A. annua are high and comparable to those when using commercial pesticides.

Biomedicine in the environment: Cyclotides constitute potent natural toxins in plants and soil bacteria

“…The variation between the controls expressed as the coefficient of variation (CV) of the controls was 8.3% for algae, 9.7% for duckweed, and 48.9% for lettuce. These variations are within the range reported in the literature [4,28,34]. The EC10 and EC50 values are listed in Table 1.…”

“…Cultivating plants that produce bioactive compounds, such as medicines, in monocultures can result in high exposure concentration of the bioactive compound to soil and water living organisms via root exudates, leaching from leaves by rain, and decomposition of plant residues affecting the local environment. As recently shown for the antimalarial crop Artemisia annua L. and cruciferous plants, bioactive compounds produced by plants can be transferred to the soil environment and affect organisms living in soil [3,4]. In addition, the transfer of bioactive compounds to the soil environment from genetically modified crops has been shown for the insecticidal Bacillus thuringiensis (Bt) toxins from transgenic corn and human serum albumin from transgenic tobacco [5,6].…”

An Endophytic Pseudonocardia Species Induces the Production of Artemisinin in Artemisia annua

“…Artemisinin is a phytoalexin, which has allelopathic effect and defends plants against herbivores and exogenous microbes [29], [30]. Both arbuscular mycorrhizal fungi and endophytic fungi have been reported to enhance artemisinin accumulation [18].…”

LC–UV/MS quality analytics of paediatric artemether formulations

“…Current analytical techniques describe derivatisation-based methods [22] , gas chromatography (GC) [23] , thin layer chromatography (TLC) [24] , supercritical fluid chromatography (SCFC) [25] , spectroscopic [26] and immunological techniques [27] , [28] , but it is clear that the main-stream methods are mainly based on high performance liquid chromatography (HPLC), coupled to ultra violet (UV), evaporative light scattering detector (ELSD), electron capture detection (ECD) or electrospray ionisation (ESI)–mass spectrometry (MS) detection [29] , [30] , [31] , [32] . Up till now, the focus was directed to biological matrices like plasma for pharmacokinetic information [33] , [34] , to plant derived samples for production reasons [23] , [35] , [36] or for environmental eco-toxicity studies [37] , [38] . However, with the advent of a plethora of newly developed 1,2,4-trioxane derivatives and the urgent demand to develop suitable paediatric formulations, there is a clear need for analytical methods which are suitable for quality purposes for finished drug products (FDP).…”