Determination of nalmefene in plasma by high-performance liquid chromatography with electrochemical detection and its application in pharmacokinetic studies.
A method for measuring human plasma levels of nalmefene after oral and intravenous administration is presented. The method consists of a solid-phase extraction procedure followed by HPLC analyses. A cyanopropyl column is used for the solid-phase extraction and 60% (v/v) acetonitrile in dilute sodium pentanesulfonic acid solution for elution. The concentrated and filtered eluate is injected into the HPLC system, which is equipped with an electrochemical dual-electrode detector. A phenyl column is used in this HPLC system with a mobile phase containing 30% (v/v) acetonitrile in dilute sodium pentanesulfonic acid solution. A signal-to-noise ratio of 4.5 is obtained when a 1 ng/ml spiked plasma sample is analyzed. To determine the applicability of this method for human pharmacokinetic studies, nalmefene levels in plasma were measured at time points up to 24 h following oral and intravenous administration of 30 mg of nalmefene hydrochloride to two subjects. These studies demonstrated that the proposed method is sufficiently sensitive to study the pharmacokinetic profile of nalmefene in man.
Laboratory of Biology of Addictive Diseases, Rockefeller University, New York, NY 10021.
J Z
JZ
Chou
H
H
Albeck
M J
MJ
Kreek
D000284:Administration, Oral; D002851:Chromatography, High Pressure Liquid; D004563:Electrochemistry; D006801:Humans; D007202:Indicators and Reagents; D007275:Injections, Intravenous; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics
D007202:Indicators and Reagents; D009292:Narcotic Antagonists; D009271:Naltrexone; C038981:nalmefene