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.
journal_name
J Pharm Biomed Analjournal_title
Journal of pharmaceutical and biomedical analysisauthors
Oswald S,Schumacher G,Siegmund Wdoi
10.1016/j.jpba.2011.08.016subject
Has Abstractpub_date
2011-12-15 00:00:00pages
1079-84issue
5eissn
0731-7085issn
1873-264Xpii
S0731-7085(11)00454-7journal_volume
56pub_type
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