Compound Characterization

OpAns offers a service for the analysis of medicinal chemistry compound collections. This high throughput service determines:

1. Is the compound of interest (COI) present?
2. What is the purity of the sample?
3. What is the quantity for the compound of interest?

Most often this service is engaged to answer the following questions:

• What is the quality of each sample in the collection?
• Which samples should be discarded?
• Which scaffolds or compound classes have degraded?
• Which samples should be prioritized for screening follow-up?
• Which suppliers provide quality compounds in the expected amount?
• Are there issues with sample handling/logistics?

The ability to simultaneously determine both qualitative and quantitative analytical results can shine a light on the compound logistics and screening process that has been in the dark until now. This light can verify or nullify dozens of assumptions in the screening process. Typically, these assumptions fall into five areas.

1. The quality of the submitted sample.
2. The process of dissolving and storing the compound. 3. The integrity of the stored compound.
4. The process of retrieving and dispensing the compound.
5. The process of diluting and screening the compound.

We have analyzed nearly one million different compounds since 1996 using a system that gives both qualitative and quantitative results. The system involves fast HPLC followed by simultaneous on-line detection by: diode array UV detection, evaporative light scattering detection, chemiluminescent nitrogen detection, and mass spectrometry. While generation of data requires a systematically optimized system, the real challenge is reducing the data to answers. We have developed proprietary software systems to process this data and return answers.

Why OpAns?

OpAns focus is on supporting early drug discovery for high-throughput qualitative and quantitative analysis. We have the chemistry knowledge, the LC-MS/MS experience and the flexibility to develop optimized methods for analyzing your compound. Our team’s experience results in:

1. Quality Chromatography
The components of each sample must be separated to enable an accurate determination of purity and quantity. Retaining early eluting compounds and separating closely related impurities is the foundation of quality results. From the time he built the first ultra high pressure liquid chromatography system in Jim Jorgenson’s lab, Ken Lewis has been developing the fastest high quality separations possible. His combination of customized systems and optimized methods delivers the best balance of resolution, speed and detection possible.
2. Accurate Quantification
Sometimes having a ballpark idea of the sample concentration is sufficient. In those cases quantification by ELSD or a Corona detector is sufficient. OpAns can provide this quick approximate quantification. However if accurate quantification without reference standards is needed, then the detector of choice is the CLND. Dr. Lewis has more experience with HPLC-CLND than anyone else. He has had a LC-CLND in his lab since their inception in 1996. He has owned more instruments and analyzed more samples than anyone else. Before starting OpAns, his lab contained nearly 10% of the CLND systems in service in the world.
3. Reliable Results
There are many ways to generate sample characterization data. In the end, how the data was generated is immaterial. The results are what matter. Was the compound of interest present? What was the purity and quantity? An accurate high-throughput commercial system to reduce data to these answers does not exist. That is why the staff at OpAns has built a custom solution for this very purpose. Using these custom solutions OpAns can return the raw data, the processed data and the results in a host of ways ranging from simple Excel files to enterprise wide database driven solutions.

Our team has over 20 years of experience performing and interpreting these types of measurements. We know how to deliver the right balance of quality, speed, and cost enabling you to work on other projects.

Typical Analysis Conditions

Frozen DMSO samples are received in microtiter plates (384 well preferred). The sample concentration is usually between 0.1 and 10 mM with a minimum volume of 15 or 30 microliters for V-bottom 384 or 96 well plates. A water/methanol gradient with 0.1% TFA modifier is used to elute the sample off of a C18 column. A standard test mix is injected every 32 samples to confirm system suitability. Each test mix injection is evaluated for peak capacity, concentration and signal to noise. Standard QC conditions require a UV peak capacity >60 (peak width at 10% height/gradient time) and measured concentration within 10% of the actual concentration. Data is deemed acceptable only when the test samples are within tolerances.

Results

OpAns Analytical Studio is a proprietary software suite for processing our customers LC-MS data. The system performs all of the processing from the raw data (peak picking, baseline estimation, integration, spectral processing). It then applies a proprietary interpretation algorithm to determine if the intended compound is present. All samples that were determined to be of low quality are manually reviewed to give an additional assurance that the results are accurate. Finally, the results are delivered in any combination of a variety of formats (Excel, RPT, XML, Web Services) to meet our customers needs.