Domo arigato, Mr. Roboto: Leveraging automation in a generalist discovery DMPK environment

ANYL 343

Andreas Harsch, andreas_harsch@merck.com, Garrett R Ainslie, Adam H Brockman, Sujal V Deshmukh, Julie E Hamill, Sue E Hill, Naim Nazef, Lin Xu, and Gloria Y Kwei. Drug Design & Optimization, Merck Research Laboratories Boston, 33 Avenue Louis Pasteur, Boston, MA 02115
Early and relevant assessment of small molecule DMPK properties plays a pivotal role in the drug discovery process at Merck Research Laboratories Boston. Our group has adopted a generalist support approach, wherein each staff member performs a full breadth of DMPK activities. Therefore, we faced the challenge of developing versatile, generic, scalable, and cost-effective lab processes amenable to a diverse workload. This proposed operational framework favors broad implementation of automated processes, both for liquid handling and LC-MS driven data analysis. Herein, we discuss the realization of this integrated support philosophy at MRL Boston. One multifunctional liquid handling system is currently employed for fully automated work-up of all in vivo samples, as well as for execution of all key in vitro DM assays. For quantitative analysis, all generated samples funnel into multi-channel LC-MS systems enabled for automated compound tuning, data acquisition, and analysis. This liquid handling/LC-MS instrument nucleus has been successfully deployed for rapid and flexible compound evaluation against the major in vivo and in vitro decision-driving discovery DMPK parameters.