Simultaneous quantitation of the BACE1 inhibitor AZD3293 and its metabolite AZ13569724 in human matrices by LC-MS/MS
Yan Li1, Paul H Severin2, Mark R Hoffmann2
1Early Clinical Development, IMED Biotech Unit, AstraZeneca, Waltham, MA, USA 02451.
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.
