A simple and sensitive liquid chromatography method for the determination of low dihydrocodeine concentrations in human plasma: its application in Chinese healthy volunteers

Abstract

A simple, sensitive and modified method was developed for determination of low dihydrocodeine (CAS 125-28-0) concentrations in human plasma by high performance-liquid chromatography (HPLC) with diode array detector. Measurement was performed on a Zorbax XDB-C₁₈ analytical column together with a XDB-C₁₈ precolumn at 40°C after a simple one-step extraction. An isocratic mobile phase consisting of acetonitrile-0.1% trifluoro-acetic acid (TFA)-water (12:40:48, v/v/v), was run at a flow rate of 1.0 mL/min. Good chromatographic separation was achieved in less than 6.2 min. This assay was linear over a concentration range of 2.50-100 ng/mL with a lower limit of quantification at 2.50 ng/mL. The intra-and inter-day precision (relative standard deviation) was less than 6.00 and 6.62%, respectively, at all concentration levels studied, while the intra- and inter-day accuracy was 1.50–3.73% and −1.35–1.92%, respectively. Recoveries were 76.10–83.81% with coefficients of variation of 1.86–6.93%. Stability of dihydrocodeine in plasma proved to be good. The validated method was successfully applied to a bioequivalence study of dihydrocodeine after a single oral administration of 20 mg dihydrocodeine tartrate in Chinese healthy male volunteers.

Key words

Dihydrocodeine - Diode array detector - HPLC - Plasma concentration - Semisynthetic opioid

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