Merck Investigates Alternative Strategies: An Interview about DMSO Hydration
The Merck High Throughput Research Facility investigates alternative compound management strategies. One of these is DMSO Hydration. Today we talk to Ed Hudak, Sr. Research Engineer at Merck & Co, where research is being done to saturate DMSO – and the findings are promising. He joins us to investigate points to consider in DMSO hydration.
Pharma IQ: At the research facility, I understand that Merck looks to actually saturate DMSO, and have found that this works just as well or better than 100% DMSO with automated systems. Can you tell us a bit about this?
E Hudak: What we do here at our facility is that a lot of the compound plates will sit on a robotic platform for extended periods of time from days, to weeks, to months, and as we all know, the hydroscopic effects of DMSO with the uptake of water or the evaporation of the sample will cause the column heights of the sample to change in a compound plate. Thus what we at Merck do with the samples that are placed on the compound platforms, or the robotic platforms, is to saturate with DMSO so that it remains at a constant column height for the robotic platforms for pin tool transfers into the assay plates. We’ve also found that for the acoustic liquid handlers that we use,from EDC, the ATS100s that there is no difference in the amplification that we need touse to transfer 100% or saturated DMSO from the compound plate to the assay plate.
Pharma IQ: So what are the implications for long-term storage versus fresh samples?
E Hudak: So for long-term storage, the samples are sent to us from a central repository and the samples are created in 100% DMSO and so they’re shipped to us as 100% DMSO which we store from a long-term perspective in making compound plates to the robotic platforms, but what we also do is in conservation of our consumables, we will make a year’s worth of compound plates for any given robotic system, and those plates will be used throughout the course of a year so no plate is used for longer than a year for any robotic system which contains water.
Pharma IQ: And where may the sample crash or precipitate out?
E Hudak: So in studies we have done we have tested samples that we had stored here for two years, and freshly made samples. We did a study to see: is there any difference with a freshly-made sample versus a sample stored in water from a mass spec perspective? And we found that there was relatively little difference in 100% DMSO versus a sample that had been stored in a saturated DMSO content for up to two years. What we have seen is that if a sample is going to precipitate, it’s going to precipitate within the first week of being put into the solution, and whether that is 100%, or 75/25% DMSO/Water (saturated DMSO) value, it’s going to precipitate out very quickly and you’re not going to see it anyways.
Pharma IQ: And what are the industry standards and best practices from both perspectives?
E Hudak: It’s a cultural view from my perspective. Some people and companies want to ensure that no water is put in their compound collection and so they will do everything they can to prevent water uptake in their compounds. This requires enclosures with nitrogen purges or inert gases to remove all water from the environment which the samples are stored to the extreme. We don’t have those mechanisms in place with all of our robotic systems, and those mechanisms are not in place at every step of the work stream of putting the sample into solution, transferring it to another site, reformatting it for a robotic system, and then the robotic system using it for an extended period of time.
So there would be a lot of infrastructure needed to ensure that, or to minimise any potential for water uptake in these samples. So from our perspective, we saturate it and we allow it to remain stable for as long as possible while we’re using it.
Interview conducted by Amber Scorah.