کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1222066 | 1494659 | 2013 | 7 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: LC–MS/MS bioanalytical method development for AMG 900: Resolution of an isobaric interference in rodent in vivo studies LC–MS/MS bioanalytical method development for AMG 900: Resolution of an isobaric interference in rodent in vivo studies](/preview/png/1222066.png)
AMG 900 is an orally available small molecule that is a highly potent and selective pan-aurora kinase inhibitor currently in development for the treatment of advanced human cancers. A co-eluting, isobaric interference was discovered in preliminary LC–MS/MS analyses of rodent in vivo pharmacokinetic samples during preclinical evaluation of AMG 900. The interference was identified as a major circulating N-oxide metabolite which partially converted to an [M+H−O]+ ion under the conditions of atmospheric pressure chemical ionization. A selective liquid chromatography–tandem mass spectrometry method for the simultaneous quantification of AMG 900 and its N-oxide metabolite in plasma was developed and successfully applied for the bioanalysis of discovery stage preclinical rodent pharmacokinetic studies.
► Isobaric interference found in LC–MS/MS analyses of AMG 900 in rodent plasma.
► Interference identified as APCI in-source conversion of N-oxide metabolite.
► LC–MS/MS method for quantitation of AMG 900 and N-oxide metabolite was developed.
► Method was successfully applied for quantitation of AMG 900 in preclinical studies.
Journal: Journal of Pharmaceutical and Biomedical Analysis - Volume 74, 23 February 2013, Pages 171–177