Two Assays for Dihydrocodeine in Plasma and in Urine and Their Use to Determine the Bioavailability of a Controlled-Release Product

Abstract

AbstractA GC method (20 ng/mL quantitation limit) and an HPLC method (37.5 ng/mL quantitation limit) for the analysis of dihydrocodeine in plasma and an HPLC method for dihydrocodeine in urine (2 μg/mL quantitation limit) are described. These methods have been used to compare the bioavailability in four subjects of a controlled-release formulation of dihydrocodeine bitartrate (equivalent to 90 mg of base) with that of a solution (equivalent to 3 × 30 mg of base). With each preparation, the mean urinary recovery of dihydrocodeine was ~30 mg, and both had a comparable bioavailability. A further study with 12 subjects, each taking the equivalent of 30 mg of base at 12 hourly intervals for 4 d, indicated that the controlled-release formulation produced effective steady-state concentrations of drug whether administered before or after meals, with no accumulation being observed.