کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1213591 | 1494139 | 2012 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Quantitative determination of odanacatib in human plasma using liquid–liquid extraction followed by liquid chromatography–tandem mass spectrometry analysis Quantitative determination of odanacatib in human plasma using liquid–liquid extraction followed by liquid chromatography–tandem mass spectrometry analysis](/preview/png/1213591.png)
Odanacatib (ODN, MK-0822) is an investigational drug under development for the treatment of osteoporosis. A quantitative LC/MS–MS methodology was developed and validated to determine ODN concentrations in human plasma, with a linear calibration range from 0.500 to 500 ng/mL. Stable isotope 13C6-labeled ODN was employed as the internal standard (IS). Sample preparation was based on liquid–liquid extraction of basified plasma with methyl t-butyl ether in a 96-well plate format. The extracted samples were analyzed on a liquid chromatography–tandem mass spectrometry system equipped with a turbo ion spray source. Chromatographic separation of the analyte and IS was achieved on a Phenomenex Luna C18 (50 mm × 2.0 mm, 5 μm) column. Ion pairs m/z 526 → 313 for the analyte and m/z 532 → 319 for the IS were monitored in positive ionization mode for MS detection. This methodology has been fully validated and proved to be rugged and reproducible. Intra- and inter-run variability was within 5.88%, with accuracy between 95.6 and 106% of the nominal concentrations. Analyte stability was evaluated under various sample preparation, analysis and storage conditions. This assay has been utilized to analyze human plasma samples obtained from phase I to III clinical trials.
► An LC/MS–MS assay was developed to measure odanacatib concentrations in human plasma.
► Sample preparation was based on automated liquid–liquid extraction.
► The linear calibration range was from 0.5 to 500 ng/mL.
► Assay precision was within 5.88%, and accuracy was between 95.6 and 106%.
► The methodology was fully validated and widely applicable to clinical bioanalysis.
Journal: Journal of Chromatography B - Volumes 885–886, 15 February 2012, Pages 15–23