کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1213987 | 966913 | 2010 | 5 صفحه PDF | دانلود رایگان |
This manuscript describes the determination of the nociceptin/orphanin FQ peptide (NOP) receptor agonist RO0646198 in rat and Cynomolgus monkey plasma using liquid chromatography coupled to tandem mass spectrometry. The structural analogue RO0658791 served as internal standard. After protein precipitation with ethanol, clean up and enrichment was carried out by on-line solid-phase extraction on a 10 mm C18 trapping column. Gradient separation was performed on a 50 mm C18 analytical column, followed by electrospray ionization and detection in positive ion selected reaction monitoring (SRM) mode. The total run time was 2.5 min. The lower limit of quantification (LLOQ) was 10 pg/mL. Precisions were below 19% and accuracies were between 86% and 118%. The recoveries were above 90%, and no significant matrix effect was observed. The method was successfully applied to low dose pharmacokinetic studies. The bioavailability after oral dosing was below 5% for rats and below 1% in Cynomolgus monkeys, limiting the application of RO0646198 in the clinic to parenteral routes.
Journal: Journal of Chromatography B - Volume 878, Issue 23, 1 August 2010, Pages 2101–2105