Purity Assessment by LC/MS

Is the Composition of Your Compound Library a Concern?

Extensive libraries of chemical compounds maintained or purchased by many pharmaceutical and some biotech companies require periodic testing to ensure consistent quality.
Before screening the libraries it is often recommended to conduct an analytical evaluation to ensure the presence of the expected compound. High-throughput (HT) or "attended HT" batch testing is frequently used, resulting in bottlenecks in data review and interpretation.
A software solution from ACD/Labs uses LC/MS data and other available analytical results to confirm the compound presence in real time, and incorporate the results into the company's informatics infrastructure that might also contain the biological screening data. This ensures that the results from the samples with questionable composition are separated from further discovery research, and conclusive decisions can be made quickly.

How Does This Work?

Based on the mass of the compounds that are expected to be in the sample, their presence is confirmed by LC/MS screening and software analysis. The degree of purity is then determined based on the UV data. Results from a variety of instrumentation hardware can be combined to get the final confirmation that is transferred to the informatics system in an automated fashion.
ACD/Labs software uses all of the information in the mass spectrum, such as expected ¹²C/¹³C isotope ratios, to confirm the presence of a known component. This approach greatly reduces the number of false-positive compound confirmations due to isobaric interferences. Experts can find out more about ACD/Labs componentization algorithms from the following poster presented at ASMS 2006).
Since ACD/Labs analytical software is known for its ability to process data from a wide range of instrument types, it becomes possible to use all of the analytical information collected in a heterogenic, multi-instrument laboratory. To complement the real-time analysis and delivery of the analytical results, the software will generate custom reports as per users' specification, and is flexible to be integrated into a variety of custom HT processes.

What Are the Real World Applications of This Solution?

ACD/Labs users have discussed the results of testing this software in their high-throughput settings at the ACD/Labs' ASMS Seminars in 2005 and 2006.

Impurity and Metabolite Identification and Confirmation—in HT

The software has also been tested to automate qualitative analysis and confirmation of chemical structures in environments such as impurity and metabolism identification, natural product dereplication by LC/MS, and high-throughput purification in pharmaceutical development.
In several pilot deployments, full scan LCMS data and ACD/IntelliXtract software are used to automatically extract all chromatographic components, assign the [M+H]⁺ or [M-H]^- for each, and then flag known compounds, expected metabolites, or impurities. Processed results for both known and unknown components are clearly summarized, and sent to the analyst for review, making it faster and easier to identify the new components of interest.

If compound library evaluation in a high-throughput environment, or automated impurity confirmation and identification, are among your concerns, please contact us to discuss available software solutions by e-mailing ms@acdlabs.com or contacting your account manager or distributor.