An integrated bioanalytical method development and validation approach: case studies |
| |
Authors: | Xue Y-J Melo Brian Vallejo Martha Zhao Yuwen Tang Lina Chen Yuan-Shek Keller Karin M |
| |
Affiliation: | Celgene Corporation, Summit, NJ, USA. yoxue@celgene.com |
| |
Abstract: | We proposed an integrated bioanalytical method development and validation approach: (1) method screening based on analyte's physicochemical properties and metabolism information to determine the most appropriate extraction/analysis conditions; (2) preliminary stability evaluation using both quality control and incurred samples to establish sample collection, storage and processing conditions; (3) mock validation to examine method accuracy and precision and incurred sample reproducibility; and (4) method validation to confirm the results obtained during method development. This integrated approach was applied to the determination of compound I in rat plasma and compound II in rat and dog plasma. The effectiveness of the approach was demonstrated by the superior quality of three method validations: (1) a zero run failure rate; (2) >93% of quality control results within 10% of nominal values; and (3) 99% incurred sample within 9.2% of the original values. In addition, rat and dog plasma methods for compound II were successfully applied to analyze more than 900 plasma samples obtained from Investigational New Drug (IND) toxicology studies in rats and dogs with near perfect results: (1) a zero run failure rate; (2) excellent accuracy and precision for standards and quality controls; and (3) 98% incurred samples within 15% of the original values. |
| |
Keywords: | bioanalytical method LC‐MS/MS stability matrix effects ruggedness |
本文献已被 PubMed 等数据库收录! |