A bioanalytical strategy utilizing dried blood spot sampling and LC-MS/MS in discovery toxicology studies

被引:0
|
作者
Discenza, Lorell [1 ]
Obermeier, Mary T. [1 ]
Westhouse, Richard [1 ]
Olah, Timothy V. [1 ]
D'Arienzo, Celia J. [1 ]
机构
[1] Bristol Myers Squibb Co, Dept Pharmaceut Candidate Optimizat, Princeton, NJ USA
关键词
DBS;
D O I
10.4155/BIO.12.69
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Background & Method: The small sample volumes characteristic to dried blood spot (DBS) sampling enabled us to right-shift the linear dynamic range of an LC-MS/MS plasma assay tenfold and eliminate the need for extensive sample dilution in support of three discovery toxicology studies in which both plasma and DBS samples were collected. With the right-shifted DBS assay range, no DBS study samples required dilution, while all of the plasma samples were diluted 5-50-fold. Results: DBS standard curves from 78-80,000 nM were linear, the performance of the curve and QC samples was within acceptable discovery-assay criteria and individual plasma and DBS data were comparable. Linear correlations of C-max and AUC derived from DBS and plasma data resulted in R-2 > 0.9. Conclusion: This bioanalytical strategy represents a benefit to the bioanalyst that can expedite the return of data and minimize the potential for error and variability that can result from extensive dilutions of study samples.
引用
收藏
页码:1057 / 1064
页数:8
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