Application of a sensitive liquid chromatographic/tandem mass spectrometric method to pharmacokinetic study of nalmefene in humans

摘要

A sensitive, specific and rapid liquid chromatographic/tandem mass spectrometric (LC/MS/MS) method was developed and validated for quantification of nalmefene in human plasma. An aliquot of 200 mu L plasma sample was simply precipitated by 400 mu L methanol. Separation of nalmefene and the internal standard hydromorphone from the interferences was achieved on a C-18 column followed by MS/MS detection. The analytes were monitored in the positive ionization mode with a Turbolonspray source. The method had a total chromatographic run time of 4.5 min and linear calibration curves over the concentration range of 10-5000 pg/mL. The lower limit of quantification (LLOQ) was 10 pg/mL. The intra- and inter-day precision was less than 10.1% determined from QC samples at concentrations of 30, 300 and 4500 pg/mL, and the accuracy was within +/- 3.4%. As the method was more sensitive (10 times higher) than those reported previously, we investigated the pharmacokinetics of nalmefene in healthy volunteers after a single intravenous injection of low dose (30 mu g) of nalmefene hydrochloride for the first time. (c) 2007 Elsevier B.V. All rights reserved.