title: Quantitative determination of methylnaltrexone in human serum using liquid chromatography-tandem mass spectrometry.
abstract: Methylnaltrexone (MNTX) is a novel peripherally acting μ-opioid antagonist that prevents peripheral side effects of opioid drugs such as constipation without affecting the analgesia. We developed a selective and sensitive assay to measure MTNX concentrations in human serum. The drug was measured after protein precipitation with perchloric acid using naltrexone as internal standard and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for detection. The chromatography was performed isocratically on a RP18 column using 25 mM ammonium acetate buffer (pH 4)/acetonitrile (90%/10%; flow rate 200 μl/min) as mobile phase. The MS/MS analysis was performed in positive ionization mode monitoring the m/z transitions 356.4/284.2 for MNTX and 342.4/324.2 for naltrexone. The method was validated according to selectivity, linearity, accuracy, precision, recovery, matrix effects and stability. The validation range for MNTX in serum was 0.5-250 ng/ml. The developed LC-MS/MS was shown to be valid and successfully applied to measure serum-concentration-time curves of MNTX in a pilot study in healthy volunteers.
authors: Department of Clinical Pharmacology, Ernst-Moritz-Arndt University Greifswald, Friedrich-Loeffler-Str. 23d, 17487 Greifswald, Germany. stefan.oswald@uni-greifswald.de
authors: Stefan
authors: S
authors: Oswald
authors: Gitta
authors: G
authors: Schumacher
authors: Werner
authors: W
authors: Siegmund
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D009292:Narcotic Antagonists / Q000097:blood* / Q000493:pharmacokinetics; D000644:Quaternary Ammonium Compounds / Q000097:blood / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D009292:Narcotic Antagonists; D000644:Quaternary Ammonium Compounds; C032257:methylnaltrexone; D009271:Naltrexone