Unexpected removal of the most neutral cationic pharmaceutical in river waters

Abstract

Contamination of surface waters by pharmaceuticals is now widespread. There are few data on their environmental behaviour, particularly for those which are cationic at typical surfacewater pH. As the external surfaces of bacterio-plankton cells are hydrophilic with a net negative charge, it was anticipated that bacterio-plankton in surface-waters would preferentially remove the most extensively-ionised cation at a given pH. To test this hypothesis, the persistence of four widely-used, cationic pharmaceuticals, chloroquine, quinine, fluphenazine and levamisole, was assessed in batch microcosms, comprising riverwater and bacterio-plankton, to which pharmaceuticals were added and incubated for 21 days. Results show that levamisole concentrations decreased by 19 % in microcosms containing bacterio-plankton, and by 13 % in parallel microcosms containing tripeptide as a priming agent. In contrast to levamisole, concentrations of quinine, chloroquine and fluphenazine were unchanged over 21 days in microcosms containing bacterio-plankton. At the river-water pH, levamisole is 28 % cationic, while quinine is 91-98 % cationic, chloroquine 99 % cationic, and fluphenazine 72-86 % cationic. Thus the most neutral compound, levamisole, showed greatest removal, contradicting the expected bacterio-plankton preference for ionised molecules. However, levamisole was the most hydrophilic molecule, based on its octanolwater solubility coefficient (Kow). Overall the pattern of pharmaceutical behaviour within the incubations did not reflect the relative hydrophilicity of the pharmaceuticals predicted by the octanol-water distribution coefficient, Dow, suggesting that improved predictive power, with respect to modelling bioaccumulation, may be needed to develop robust environmental risk assessments for cationic pharmaceuticals.

Quantitative structure–activity relationships for primary aerobic biodegradation of organic chemicals in pristine surface waters: starting points for predicting biodegradation under acclimatization

“…It is known that the persistence of ionizable organic chemicals is probably attributable to the lack of uptake in cells, whereas the presumed electrostatic attraction appeared to have no measurable inuence on membrane passage. [53][54][55] For this reason, chemicals were also classied according to the chemical's speciation state (at pH $ 7.4 using pK a values from Drugbank or Chemaxon estimation). To investigate further the inuence of specic chemical characteristics on the biodegradation rate constant, class-specic QSARs were derived using linear regression and aforementioned descriptors.…”

Highly multiplexed design of an allosteric transcription factor to sense novel ligands

“…Quinine has been used since the 17 th century as an antimalarial drug and, despite its well-documented adverse side effects, is still in use today, primarily in underdeveloped countries with resource-limited healthcare systems or where safer modern alternatives are not available 40 . In such communities, significant levels of quinine are likely to be detected in the wastewater, which is often recycled for irrigation or freshwater sustainability and can carry unforeseen environmental and health ramifications 55 . Thus, an affordable biosensor for monitoring quinine metabolism and detection in water supplies may be of interest.…”

Transition-state rate theory sheds light on ‘black-box’ biodegradation algorithms

“…Phenomena not incorporated in eqn (3) whilst incorporated in the RF-QSBR and CATABOL may include differences in test conditions needed for heterogeneous (dissimilar) chemicals (e.g. toxicity or solubility), ion trapping, 27,123,124 non-linear sorption, co-metabolism, size exclusion 100,101 and a diversity of active uptake routes for heterogeneous (dissimilar) chemicals.…”