Simultaneous quantitation of the BACE1 inhibitor AZD3293 and its metabolite AZ13569724 in human matrices by LC-MS/MS.
| Autor: | Li Y; Early Clinical Development, IMED Biotech Unit, AstraZeneca, Waltham, MA, USA 02451., Severin PH; Clinical Laboratories, Covance Laboratories, Inc., Madison, WI, USA 53704., Hoffmann MR; Clinical Laboratories, Covance Laboratories, Inc., Madison, WI, USA 53704., Miller DL; Clinical Laboratories, Covance Laboratories, Inc., Madison, WI, USA 53704., Monk SA; Drug Disposition, Lilly Research Laboratories, Eli Lilly & Company, Indianapolis, IN, USA 46285., Kugler AR; Clinical Pharmacology, Coastal Pharma Group, Concord, MA, USA 01742. |
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| Jazyk: | angličtina |
| Zdroj: | Bioanalysis [Bioanalysis] 2017 May; Vol. 9 (10), pp. 813-826. Date of Electronic Publication: 2017 Apr 24. |
| DOI: | 10.4155/bio-2017-0003 |
| Abstrakt: | Aim: AZD3293 is a novel BACE1 inhibitor in Phase III development for Alzheimer's disease. Sensitive and robust bioanalytical methods were required to quantitate AZD3293 and its metabolite AZ13569724 in human biological matrices. Methodology/results: Human plasma was prepared by protein precipitation. Linearity for both analytes was in the range of 0.5-500 ng/ml with up to 100-fold dilution. Plasma ultrafiltrate samples were prepared using Centrifree ® ultrafiltration device. Urine and CSF samples were analyzed directly after dilution. A 27% decrease in AZD3293 concentrations in the CSF collection apparati was found due to nonspecific binding. Incurred sample reanalysis was acceptable. Conclusion: Methods for simultaneous quantitation of AZD3293 and its metabolite AZ13569724 in human biological matrices have been validated and successfully applied to clinical studies. |
| Databáze: | MEDLINE |
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