title: Environmental fate and chemistry of raloxifene hydrochloride.
abstract: Raloxifene hydrochloride is a selective estrogen receptor modulator (SERM) used for the prevention and treatment of osteoporosis in women. Excretion of raloxifene occurs through the feces of patients. Raloxifene has the potential to be discharged into waste treatment systems after therapeutic use. Raloxifene hydrochloride was investigated using a battery of studies designed to describe its physical/chemical characteristics and define its fate in the environment. The mean measured solubility of raloxifene hydrochloride (+/- standard deviation) was 345.2 +/- 15.6 microg/ml, 13.3 +/- 0.6 microg/ml, 0.9224 +/- 0.015 microg/ml, and 627.4 +/- 132.0 microg/ml in aqueous buffers at pH 5, 7, and 9 and in unbuffered water, respectively. Raloxifene exhibited a mean molar absorptivity of 34,000 and a wavelength absorbance maximum at 287 nm for pH 5 and 7 aqueous buffer solutions and 297 nm at pH 9. Mean measured Kow values were 516 +/- 17, 1,323 +/- 91, and 1,556 +/- 135 at pH 5, 7, and 9, respectively. After 5 d at 50 degrees C, raloxifene hydrolyzed 8.02, 10.61, and 23.81% in pH 5, 7, and 9 aqueous buffers, respectively. In a 28-d hydrolysis study at 25 degrees C, the calculated first-order hydrolysis rates were 6.92 x 10(-4), 1.70 x 10(-3), and 7.66 x 10(-3)/d, and the corresponding half-lives were 1,001, 410, and 90 d in pH 5, 7, and 9 aqueous buffers, respectively. Raloxifene sorbed significantly to sewage treatment solids with Freundlich isotherm adsorption coefficients K between 2,000 and 3,000. Raloxifene degraded rapidly in the presence of sewage solids. In a system containing 0.470 g/L sludge solids, the raloxifene biodegradation rate and half-life were 0.0966/h and 7.17 h, respectively. In a 28-d aerobic-aquatic biodegradation study containing 30 mg/L sludge solids, the raloxifene biodegradation rate and half-life were 0.0188/d and 37 d, respectively. Given the fate and behavior of raloxifene in these studies, it is anticipated that raloxifene would rapidly dissipate in the environment.
authors.affiliation: Lilly Research Laboratories, Division of Eli Lilly and Company, Greenfield, Indiana 46140, USA. jsteeter@lilly.com
authors.forename: Jerold Scott
authors.initials: JS
authors.lastname: Teeter
authors.forename: Roger D
authors.initials: RD
authors.lastname: Meyerhoff
mesh_terms: D001673:Biodegradation, Environmental; D004784:Environmental Monitoring; D005243:Feces; D006207:Half-Life; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020849:Raloxifene Hydrochloride / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D012037:Refuse Disposal; D020845:Selective Estrogen Receptor Modulators / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D012995:Solubility; D014874:Water Pollutants, Chemical / Q000032:analysis*
chemical_list: D020845:Selective Estrogen Receptor Modulators; D014874:Water Pollutants, Chemical; D020849:Raloxifene Hydrochloride