Tox Chat Box: Decoding forensic toxicology with LC-MS/MS

Dr. Karl Oetjen is a Senior Scientist at SCIEX in the technical marketing group and has over 10 years of mass spectrometry experience. Before joining SCIEX, he completed his PhD at Colorado School of Mines (Golden, Colorado) in Hydrologic Science and Engineering. Since joining SCIEX, Karl has worked with numerous labs creating and implementing both regulated and unregulated quantitative and qualitative screening methods.

Pierre Negri (P.N.): Welcome to the first episode of Tox Chat Box, a SCIEX Vodcast series where we discuss the latest trends and applications in forensic toxicology.

I am Pierre Negri from SCIEX. And in today's episode, we are going to discuss the use of accurate mass spectrometry for drug screening and identification of unknown substances. And today we are joined by SCIEX’s own Karl Oetjen. Karl is a senior scientist on the North American marketing team. Hey, Karl. How is it going?

Karl Oetjen (K.O.): Good, Pierre. Thanks for having me.

P.N.: So, Karl. Can you tell us more about your scientific background, what you do at SCIEX in your current role, and most importantly, what you enjoy the most about working in this field?

K.O.: Yes. So, I have been doing mass spectrometry for over ten years now, starting in oil and gas, where we were doing a lot of unknown research, looking for compounds and how they are changing as they returned up whole from hydraulic fracturing. So, that has to be my favorite part, right? It is figuring out what the unknown compound is. So, going from a feature to an ID. But since I have joined SCIEX, I started in applications where I was doing customer training, before moving into this role, three years ago or so, where I focus much more on customer collaborations, and creating scientific content.

P.N.: So, you being an accurate mass expert is actually very fitting, right? Because today I want to have you on the vodcast to discuss the use and the benefits of accurate mass spectrometry, more specifically for drug screening, and characterization of unknown substances. So, can you describe some of the benefits of accurate mass for those types of workflows?

K.O.: Yes, definitely. When I think of the major benefit of accurate mass for those types of workflows, it would be adding confidence. So, moving from a triple quadrupole or nominal mass, where, you know, the mass error is within 0.7 Daltons to an accurate mass system where we are talking much of the fourth decimal place is huge. We can become really confident in the compound we are looking for. And that can allow us to see through the noise of interferences, but be sure when we say this is, in fact, this, that we can be confident and put a gold star on it.

P.N.: Now, you and I have been going to a lot of forensic toxicology trade shows over the past couple of years. And I think you would agree that we have seen a great uptake in accurate mass adoptions over the past couple of years in the forensic toxicology community and precisely for the reasons that you mentioned. There is a lot of screening workflows that require identification of unknown substances or new substances. And I think you would also agree that we have seen a lot of our customers really digging into that data and really screen for additional candidate precursors, more specifically using diagnostic ion screening. So, I know you are the expert in the field, so I wanted to ask you if you could share some insights on the benefits of this approach, really to benefit the streamlining process for drug screening and also maybe cover some of the potentials for the identification of drug biomarkers in biological samples.

K.O.: Yes, definitely. We have certainly seen high resolution mass spectrometry increasing the amount of usage in the forensics field. Over the past, let’s say five years, it seems like it is almost tripled. And one of the tools that we can try to use to better characterize our chemical space is diagnostic ion screening. So, diagnostic ion screening is really taking a compound that you know something about: you know one of its diagnostic ions at least, maybe two, maybe three. And interrogating your data set to find what features have those diagnostic ions. And then after that, you can try to figure out what they are, but you have already got a huge clue. You know, it is related to your parent compound.

P.N.: So, you mentioned diagnostic ion screening being more and more prevalent, right. We have seen also an uptake in our users using Molecule Profiler, which is a software tool that is directly integrated into SCIEX OS software. And I was wondering if you could describe your experience processing accurate mass data using Molecule Profiler and more specifically to do retrospective analysis on previously acquired data sets and the type of information that you can extract from that from that platform.

K.O.: Yes, definitely. So, Molecule Profiler is a tool within SCIEX OS that you can use to basically say, here is the compound I am interested in. Take fentanyl for example. So, here's fentanyl, here is its structure, here is its MS/MS spectra. And Molecule Profiler will go in and say great, now tell me what data set you want to query and for what you want to query it. And in this case, we are talking about diagnostic ions. So, I might say, hey I want to find any feature that has that 105-ion. And I want you to list it for me. So, a data set that might have contained 5000 different features in a complex matrix like blood now contains 20 of compounds or features of interest, that contain those ions, that are related to fentanyl. So, it is a great way to shrink your list down and save some time.

P.N.: Great Karl, it is really good information. And that is a wrap for today's episode on the use of diagnostic ion screening using Molecule Profiler for drug screening and unknown substance identification. So, a big thank you to my guest, Karl. Thank you for answering all my questions and sharing all your knowledge.

K.O.: Absolutely. Thanks for having me, Pierre.

P.N.: Awesome. And thanks to viewers for tuning in and watching this episode. As Karl mentioned, if you want to know more about the use of Molecule Profiler, please make sure to check out the software page on sciex.com. And, as Karl mentioned, I am going to share the direct links to the technical note that describes the use of this platform for the analysis of fentanyl analogs. And then, I am also going to provide a direct link to the on-demand webinar that Karl presented if you want to know more about this.

Thanks for joining us today. In the next episode, we will be joined by Doctor Alex Krotulski, who is managing the NPS Discovery program over at the Center for Forensic Science Research and Education. We will be discussing how his lab is using accurate mass spectrometry for characterization and identification of unknown novel psychoactive substances. So, we are going to be digging into how he is leveraging accurate mass and all these bioinformatic tools for the NPS Discovery program that he is spearheading. So, make sure to tune in for that. Thank you so much. And we will see you next time.