STSM on Novartis campus: Quantification in Mass spectrometry imaging
My Short Term Scientific Mission (STSM) was held for two weeks on the Novartis Campus in Basel, Switzerland. I was working in the Mass spectrometric imaging group of Markus Stoeckli; my practical supervisors were Dieter Staab and Gregory Morandi. I visited the campus for two main reasons; I wanted to learn the quantification in mass spectrometry imaging (MSI) and I wanted to explore research lab in a pharmaceutical company.
If your are a regular reader of this blog, you might know I am a PhD student of Pharmaceutical analysis at Charles University in Prague at the moment being on an internship at FOM Institute AMOLF in Amsterdam. LC/MS development of methodologies for quantification of pharma compounds is my domain in the Czech Republic and at AMOLF I am working on projects involving MSI. The quantification in MSI was therefore a challenge to learn and a missing junction between my two research areas.
The Mass spectrometric imaging group at Novartis has a long experience with this MS imaging and its quantification approaches. I have a pharmaceutical background and I have always felt a strong passion for pharmacy. Novartis was therefore the ideal place for my Short Term Scientific Mission. Below you find a summary of the whole stay. More about STSM, what it is and how to apply is available also here.
During the first three days I was learning how to work with the instruments and also the basics of MSI quantification. I learned the entire workflow of a method development. The samples in this stage were provided by Novartis.
The first experiments were done with the whole body tissue sections of rats dosed with a selected drug. The rats were sacrificed one hour after the dosing and with MS imaging we were able to observe, which organs the drug got into. When a calibration curve was constructed, also concentration of the drug within each compartment could be determined.
Nevertheless, it has to be noted, that the precision and accuracy of MSI quantification is still quite low. It means there are still better methods which provide us with the information on the drug concetration. MSI has, however, several advantages. Most importantly, it combines the compound identification with its localization within tissue surface. MSI distinguishes between the parent drug and its metabolite. This is very important, as sometimes the metabolites might accumulate in other organs and cause mild to severe problems - side effects.
On this picture you can see a rat dosed with a drug (on right the front part, on left the back part). The white area is stomach and it clearly shows that our compound is accumulated there. That is in agreement with the expectations, as this particular rat was sacrificed one hour after the oral administration of the drug.
When I became more or less an independent user of the instruments and I knew, how to proceed, I started to develop a method for evaluation of pimonidazole in breast cancer tissue sections. Pimonidazole is used as a hypoxia marker in tumors. The tumor samples were delivered directly from AMOLF. I did not have luck to collect any breathtaking results, but I suceeded with the method development and the work brought me more insight into MSI quantification.
I was also introduced to another methodologies used for quantification (e.g. counting of the tissue suppression factor), but only in theory. Firstly we did not have too much time for doing real experiments and secondly it was actually found out that they are even less accurate and precise than the usual method. (Even though there are groups which apply them in practice.)
One afternoon I spent on a tour through the Novartis campus. I did not take the camera, but you can take part in your own virtual tour here. There is almost as much interesting architecture on the campus as there is interesting science. :-) More pictures are available on this link. And here is a nice article about the campus masterpiece; I call it privately The diamond building. :-)
The two weeks passed very fast, as it usually happens, when you have a lot to do. Now I am back in Amsterdam and I am looking forward to go home for couple of days during the Christmas time. In the photogallery you also find couple of pics from Basel. :-)
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July 29, 2018, 17:06 (No. 146)Lw
Tak tohle bylo velmi zajímavé počtení! Psala jsi někde i o svojí práci s LC-MS?