[Plasma pharmacokinetics of morphine and morphine-6-glucuronide using high performance liquid chromatography and...

This pilot study was undertaken in a group of 7 patients receiving morphine either by oral route under a controlled release form (Moscontin tablets), or by subcutaneous route with continuous infusion. Complete pharmacokinetics over 24 h were carried out with blood samples taken every hour. The measurements of morphine and of its metabolite, morphine-6-glucuronide (M6G) were performed by high-performance liquid chromatography (HPLC) with coulometric detection, using nalorphine (NAL) as an internal standard. The morphinics were extracted on a Bond Elut C18 column according to a double liquid-solid extraction. The extract was chromatographed by ion-pairing on a mu Bondapak C18 column, 10 microns (300 x 3.9 mm). The minimal detectable concentrations were respectively 1 and 5 ng/ml for M and M6G. When Moscontin was given at dosages < 1 mg/kg/d, the areas under the curve over 24 h (AUC 24 h) of M were rather close to those of M6G (ratio 1.1 +/- 0.1). However, with dosages > 1 mg/kg/d, a difference appeared and gradually rose to a M/M6G ratio of 1.3 +/- 0.04. With subcutaneous infusion, the plasma levels of M6G were from 2 to 17-fold lower than those of M.