Increasing scope and throughput of the Laser Diode Thermal Desorption (LDTD) technique with compound libraries.

Beattie Iain, Smith Aaron, Weston Daniel J, White Peter, Szwandt Simon, Sealey Laura "Journal of pharmaceutical and biomedical analysis"

Within the drug discovery environment, the important approach in optimising the chemistry of a structural collection toward a possible drug candidate will be the design, make and check cycle, through which the primary screens consist of a number of in vitro assays, which includes metabolic stability, cytochrome P450 inhibition, and time-dependent inhibition assays.

These assays are frequently carried out employing many drug compounds with chemically varied structural capabilities, often in a 96 well-plate format for optimum time-efficiency, and so are supported employing rapid liquid chromatographic (LC) sample introduction using a tandem mass spectrometry (MS/MS) selected reaction monitoring (SRM) endpoint, using around six.5h for each plate.

To provide a faster time-to-decision at this vital stage, there exists a necessity for greater sample throughput as well as a strong, well-characterized analytical alternative. This paper presents a comprehensive analysis of laser diode thermal desorption (LDTD), a comparatively new ambient sample ionization method, for compound screening Libraries assays.

By systematic modification of common LDTD instrumentation and workflow, and supplying deeper understanding around conquering quite a few important problems, this perform establishes LDTD as being a sensible, rapid option to standard LC-MS/MS in drug discovery, without want for extensive sample planning or expensive, scope-limiting inner specifications.

Analysis of each the five and three cytochrome P450 competitive inhibition assay samples by LDTD gave enhanced sample throughput (0.75h per plate) and provided comparable data top quality as the IC(50) values obtained were inside three fold of those calculated in the LC-MS/MS data. In addition when applied generically into a chemically diverse library of over 250 proprietary compounds from the AstraZeneca style, make and test cycle, LDTD demonstrated a good results fee of 98%.