Codeine-6-glucuronide

Abstract: Purpose. The antinociceptive and immunosuppressive effects of codeine and codeine 6-glucuronide were determined in rats after intra-cerebroventricular administration.

Abstract: The toxicodynamics and, to a lesser degree, toxicokinetics of the widely used opiate codeine remain a matter of controversy. To address this issue, analytical methods capable of providing reliable quantification of codeine metabolites alongside codeine concentrations are required. This article presents a validated method for simultaneous determination of codeine, codeine metabolites codeine-6-glucuronide (C6G), norcodeine and morphine, and morphine metabolites morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) in post-mortem whole blood, vitreous fluid, muscle, fat and brain tissue by high-performance liquid chromatography mass spectrometry. Samples were prepared by solid-phase extraction. The validated ranges were 1.5–300 ng/mL for codeine, norcodeine and morphine, and 23–4,600 ng/mL for C6G, M3G and M6G, with exceptions for norcodeine in muscle (3 – 300 ng/mL), morphine in muscle, fat and brain (3–300 ng/mL) and M6G in fat (46–4,600 ng/mL). Within-run and between-run accuracy (88.1–114.1%) and precision (CV 0.6–12.7%), matrix effects (CV 0.3–13.5%) and recovery (57.8–94.1%) were validated at two concentration levels; 3 and 150 ng/mL for codeine, norcodeine and morphine, and 46 and 2,300 ng/mL for C6G, M3G and M6G. Freeze– thaw and long-term stability (6 months at 28088C) was assessed, showing no significant changes in analyte concentrations (212 to 18%). The method was applied in two authentic forensic autopsy cases implicating codeine in both therapeutic and presumably lethal concentration levels.