Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

Click here to register for free online access

Sign In to gain access to subscriptions and/or personal tools.
Journal of Biomolecular Screening
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
1087057108323911v1
13/9/862    most recent
Right arrow References
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Fonsi, M.
Right arrow Articles by Monteagudo, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fonsi, M.
Right arrow Articles by Monteagudo, E.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

High-Throughput Microsomal Stability Assay for Screening New Chemical Entities in Drug Discovery

Massimiliano Fonsi

Department of DMPK, Istituto di Ricerche di Biologia Molecolare P. Angeletti (IRBM), Merck Sharp and Dohme Research Laboratories, Roma, Italy, massimiliano_fonsi{at}merck.com

Maria V. Orsale

Department of DMPK, Istituto di Ricerche di Biologia Molecolare P. Angeletti (IRBM), Merck Sharp and Dohme Research Laboratories, Roma, Italy

Edith Monteagudo

Department of DMPK, Istituto di Ricerche di Biologia Molecolare P. Angeletti (IRBM), Merck Sharp and Dohme Research Laboratories, Roma, Italy

In this work, the authors present a novel, robotic, automated protocol for assessing a metabolic stability protocol assembled on a Hamilton platform and a new strategy for pooling samples (cassette analysis). To increase the high throughput of the liquid chromatography (LC) step, fast chromatography and automated liquid chromatography tandem mass spectrometry (LC/MS/MS) analytical methods were also developed, and a rapid data analysis system was generated that converts peak areas obtained by LC/MS/MS in intrinsic clearance values. All of the steps of the microsomal stability assay were carefully studied and optimized. Standard errors and confidence intervals of the measured clearances were also automatically generated in the process to allow an immediate evaluation of the significance of observed values. Methods based on pooling analysis of 2 and 4 different analytes were compared with a standard method without pooling. A simple statistical treatment was used to show their equivalence. The different protocols developed were analyzed in terms of the best compromise between accuracy and high-throughput capabilities. (Journal of Biomolecular Screening 2008:862-869)

Key Words: microsomal stability • automation • cassette analysis

This version was published on October 1, 2008

Journal of Biomolecular Screening, Vol. 13, No. 9, 862-869 (2008)
DOI: 10.1177/1087057108323911
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?