Applications of the Charged Aerosol Detector in Compound Management

Abstract

Recent literature has described the exciting development of a new universal detection technology for high-performance liquid chromatography (HPLC), as well as some exploratory work on its application to quantitative measurement of solutes at millimolar concentrations. The new methodology, known as charged aerosol detection (CAD), has been recognized as a viable alternative to evaporative light-scattering detection and refractive index detection that, like CAD, respond to molecular structures independently of their absorbance, or lack thereof, in the ultraviolet region of the electromagnetic spectrum. In this article, the authors exemplify their use of CAD in-line with HPLC and mass spectrometry (MS) to provide both stand-alone and complementary information that aids decision making for sample storage and processing practices in the compound management setting. Illustrations include monitoring contaminants leached from different plate materials into the solvent dimethyl sulphoxide (DMSO) and profiling the concentrations of solutions destined for liquid storage and dispensing to assays, with the aim of improving processes.

Gradient, Contact-Free Volume Transfers Minimize Compound Loss in Dose-Response Experiments

“…Desorption of contaminants has been shown to compromise biological assay data quality. 1,2 The most common way to make a concentration gradient is via serial dilutions of a stock solution in sequential steps. One well-known problem in generating a concentration gradient is due to the compounding of error resulting from multiple transfer steps.…”

Toward Automated Interpretation of LC-MS Data for Quality Assurance of a Screening Collection

“…A number of techniques have been developed to achieve this, including (but not limited to) liquid chromatography (LC) and mass spectrometry (MS), 1 nuclear magnetic resonance, 2 and charged aerosol detection (CAD). 3 A common requirement for many of these methods is that they can be integrated into workflows characterized by automated systems capable of high throughputs. As instrumentation has become more sophisticated with the introduction of automated compound storage 4 and nanoliter dispensing, 5 so too have the demands on data handling and interpretation.…”

Capture and Exploration of Sample Quality Data to Inform and Improve the Management of a Screening Collection

“…The ratio of CAD peak area to sample molecular weight was therefore proportional to the molar concentration of sample. 12 The CAD detector was complementary to the DAD in that, in the main, it provided confirmation of the sample purity but could also provide information not available from the DAD. This was particularly true when the sample structure did not absorb in the UV detection range or where the sample was not retained on the chromatographic column but was eluted in the solvent front along with its original solvent (normally DMSO).…”

“…The control sample was a standardized solution of warfarin in DMSO, created from solid by weighing to a target concentration of 10 mM solution that was then accurately calibrated by nuclear magnetic resonance studies. 12 Each subsequent test sample analysis, which used the same instrument assembly and the same conditions for chromatography and detection, was automatically compared with the last control sample analysis. Calculation of the analyte concentration, using the relative CAD peak areas and molecular weights of warfarin and the analyte compound, respectively, was then performed and recorded using a PL/SQL function on the database, without any need for user intervention.…”

“…AstraZeneca's compound management (CM) group uses reversed-phase high-performance chromatography (HPLC) coupled to mass spectrometry (MS) with UV-DAD and charged aerosol detection (CAD) for the routine QC/QA of the corporate compound collection. 12 Although each LCMS system had been supported by an instrument-linked review software package from the manufacturer, we had observed discrepancies in the way that a peak of interest (i.e., a chromatographic fraction peak containing appropriate mass ions for the expected compound) was defined and prioritized. The preference between two possible peaks of interest in the same chromatogram, for example, could depend on which was the largest or which was the earliest to be eluted.…”