LC–MS/MS Bioanalytical Challenge: Ultra-High Sensitivity Assays

Abstract

Anne-Françoise Aubry is Director of Bioanalytical Sciences at Bristol-Myers Squibb Co., leading a team in developing bioanalytical methods for early development drug candidates in support of toxicology and clinical studies. Her main research interests are high-speed, high-resolution LC and new approaches for LC–MS/MS drug bioanalysis in regulated laboratories. Anne Aubry is on the executive board of the Eastern Analytical Symposium and on the organizing committee of the Applied Pharmaceutical Analysis and Chemical and Pharmaceutical Structure Analysis (Shanghai 2011) conferences.

The challenges of developing and running low pg/ml LC–MS/MS bioanalytical assays in a regulated laboratory are reviewed. The practical problems encountered in implementing ultrasensitive assays are less in reaching a suitable sensitivity on the instrument than in implementing procedures to control losses and contamination, eliminate matrix interferences and ensure assay robustness so that the assay can be validated to industry standards. Solutions to these problems can be found in each of the three facets of the bioanalytical assay: the sample preparation, the chromatographic separation and the mass spectrometric detection. The key to developing an ultrasensitive assay is to optimize each of these elements. Progress in MS instrumentation has been essential in our ability to reach the low pg/ml limits.

Financial & competing interests disclosure

The author of this article is a current employee of Bristol-Myers Squibb Company (BMS). All financial support for the studies reported herein was provided by BMS. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Acknowledgements

The author wishes to thank Long Yuan, Michelle Dawes, Hao Jiang and Huidong Gu for their help in generating data for this article and Mark Arnold, Jian Wang and Hao Jiang for helpful discussion on the manuscript.

Additional information

Funding

The author of this article is a current employee of Bristol-Myers Squibb Company (BMS). All financial support for the studies reported herein was provided by BMS. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.