M5 PM Marine Environmental Chemistry of Organic Pollutants
Monday, 14 November 2005: 1:50 PM - 5:30 PM in 321-323

(FER-1117-830339) Cooperative effects between salinity and dissolved organic matter on the half-life of simvastatin.

He, L.¹, Sima, L. ¹, Chandler, G.², Ferry, J.¹, ¹ Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, US² Department of Environmental Health Sciences, University of South Carolina, Columbia, SC, US

ABSTRACT- Naturally occurring dissolved organic carbon is known to experience significant aggregation across the salinity gradient encountered at the freshwater/marine interface. There is evidence that such aggregates present less-polar microenvironments that dissolved contaminants may associate with. This work addresses how the interaction between salinity, pH, and the loading of dissolved organic carbon affect the rate of hydrolysis of a lactone, the pharmaceutical simvastatin, to the corresponding hydroxy acid. A central composite experimental design was applied to examine the effects of these three variables over the pH range 5-9; a salinity range of 0-35 ppt, and a dissolved organic carbon load of 0-15 mg/L, evaluating their role as individual variables as well as possible interactions between any two of them. This design was selected as representative of the range of probable surface water conditions experienced during estuarine mixing. Over this range, it was observed that pH was by far the most important variable in predicting the hydrolysis rate of simvastatin. However, at a fixed pH (8.3) there was an apparent interaction between dissolved organic carbon and salinity (much smaller than the pH effect alone). The hydrolysis rate correlated positively with salinity or dissolved organic carbon alone, but negatively against the combined term. This is interpreted as evidence of aggregate formation at high carbon/salt loading with partitioning of simvastatin into a protected, non-polar environment either inside or on the surface of the aggregate. A quantitative model of hydrolysis rate and estimated half-live vs conditions is presented. Preliminary measurements of the gut pH of meiobenthic copepods suggest the statin will exist primarily in the closed form in the gut of the organism.

Key words: pharmaceutical, marine, hydrolysis, multivariate