An oxycodone sample containing more than 300 ppm of 14-hydroxycodeinone was dissolved in water at pH 6.0 to produce a 7.5% solution (75 mg/mL) using 4 M HCl to effect neutralization and dissolution of the oxycodone to pH 6. Sufficient solid EDTA and solid sodium thioglycolate were added to bring the concentrations of these components in the reaction mixture to 2 mM EDTA and 20 mM thioglycolate. The pH was maintained at pH 6.0, at room temperature for 2.8 hours, after which time the reaction mixture was raised to pH 9 to precipitate the oxycodone from the solution containing the thioglycolate-Michael adduct, and excess thioglycolate. The precipitated oxycodone was washed with pH 9, 0.05 M sodium bicarbonate buffer, and dissolved in ethyl acetate. The ethyl acetate solution of oxycodone was extracted with pH 9.0, 0.05 M sodium bicarbonate buffer, and the ethyl acetate removed under reduced pressure to yield oxycodone containing less than 10 ppm of 14-hydroxycodeinone.
