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

Dr. Luke Rodda is the Chief Forensic Toxicologist and Director of the Forensic Laboratory Division at the San Francisco Office of the Chief Medical Examiner where he provides toxicological interpretation, expert court testimony and oversees forensic toxicology laboratory operations for the City and County of San Francisco. Dr. Luke Rodda also holds an Assistant Adjunct Professor position at the University of California, San Francisco Department of Laboratory Medicine.

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

I’m Pierre Negri from SCIEX. And in today's episode, we're talking about the importance of software in mass spectrometry, and more specifically, we're going to discuss software features and functionalities that are enabling forensic toxicologists to streamline toxicology data processing, management and reporting. And today we're joined by Dr Luke Rodda. Luke is the Chief Forensic Toxicologist and Director of the Forensic Lab Division at the San Francisco Office of the Chief Medical Examiner. Hi Luke. How are you doing?

Luke Rodda (L.R.): Good. Hello Pierre.

P.N.: Thank you so much for coming on. I'm very, very excited to have you on. So, to kick us off, can you briefly tell us more about your lab's operations at the San Francisco Office of the Chief Medical Examiner, the jurisdiction that you serve and the type and volume of samples that you run on a daily basis?

L.R.: Yes, certainly. So, we service the whole city and county of San Francisco, although, with the office of the Chief Medical Examiner, we don't just do postmortem toxicology. We also do all the city and county's impaired driver casework, drug-facilitated crimes, and specifically, normally sexual assaults, and then any other forensic casework that requires toxicological investigations. And there can be other crimes and aggravated assaults, for example. Our caseload is obviously increased, just like many other laboratories in the United States, due to the opioid epidemic, novel drug epidemic and the challenges that are faced with that. And so, we've had a 4 to 5 times increase in accidental overdoses just in the past ten years. The challenges in impaired drivers and sexual assaults have remained and in fact, challenged us with different types of drugs needing to be detected.

P.N.: That's great. Thank you for that background. So, I really wanted to have you on the Vodcast to discuss mass spec software. I know it sounds like an odd topic, but I think one thing that really impressed me about your lab’s operations is the extent by which you leverage your mass spec software, and more specifically, all the unique features and functions that you've developed over the years and integrated into your daily casework. So, I was wondering if you could tell us more about your journey with software and the need for these custom processing and reporting functions that you've developed over the years.

L.R.: Certainly. Yeah, I was very fortunate, at the start of my career to use SCIEX LCMS as my first sort of real instrumentation, entry point to forensic toxicology. And with that, great mentors and colleagues who pioneered efforts in managing the data at that time, MRM or LC triple quad data, and processing that in a way that was highly efficient. And using that logic and ideas, I then brought that to San Francisco, you know, now eight years ago in 2016, and we created fantastic, what we call queries, to process the data in MutliQuant, at a highly efficient rate. Not just improving the time it takes to process data but decreasing the human input level of decision-making. And so, it improves the quality assurance practice. And with both quality assurance and timeliness being improved, it's a bit of a cyclical wheel, where when you improve one, you improve the other. And with that, we've been able to keep up, not only with the casework increase, but actually add, from what used to be our scope here of 50 drugs, to now, over 450 drugs on a routine basis for every case. That mitigates bias and ensures that we capture the full toxicological profile for each individual case. We have since been moving towards the new SCIEX OS platform, and that's been the next challenge is to move all those really good quality assurance and efficiency practices that we've built into our LC triple quads to the QTOF processing software.

P.N.: That's a very fascinating journey. Thank you for all the insight. I want to shift gears now and talk about the work that you've been doing with our software product management team with regards to SCIEX OS and as you mentioned, really translating all these queries and functionalities into SCIEX OS software. I was wondering if you could talk a little bit more about this collaboration and then maybe tell the audience about some of the key custom calculations, data flagging and reporting functions that you've developed in collaboration with our software development team and how it's enabling you to streamline your laboratory's operations.

L.R.: Yeah, absolutely. So, I'm blessed to have a fantastic laboratory team, staff and colleagues here. Specifically, Megan Foley and Maria Sarkisian deserve a shout-out because they're the ones who have really helped lead the efforts with the SCIEX developers in finding the way that we can manage and handle this QTOF data.

And more than ever, we've needed to be able to efficiently manage that data because it's a much bigger data set than LC triple quad. And so, it's very important that we're able to ensure the things that we've needed and used over the years have now been transitioned across. And so doing that, our team here has been working for the last 12 to 18 months, and over several versions, to get to a place where we can create our own functionalities within the system.

For example, we want to use the QTOF to report on a final toxicology report to be used as a confirmation. Now, to do that, we need to ensure that we meet certain quality assurance practices. That's a very manual process if we're to assess all 900 plus drugs that are in our scope for the QTOF. To do that, we need it to be automated. And so, we have a limit of scope and a limit of detection that's injected for every component on every single batch. And that acts as a threshold that needs to be met for a positive detection in unknown casework so that's one functionality that we do.

Automatic quality control flagging, is another feature, and it's based on our custom concentration ranges. Not just percentages but standard deviation ranges that we set and allow for. There's a range of different features, I think it's at least about 20, that we can now customize specifically to how we want to manage and control that data processing.

P.N.: Thank you so much for the insight. I know, coincidentally, you're in the middle of validating a QTOF method. So, I know how critical having those functionalities is right now for your laboratory. So, good luck to you and your team on that. And, I really looking forward to seeing where you're taking all these functions and functionalities.

So last question before I let you go. Again, thank you so much for your insights. It's very useful for us to hear customers talk about transitioning from Analyst and MultiQuant into SCIEX OS. I've seen your journey, at least for the past five years, at the office of the Chief Medical Examiner in San Fransisco. What do you think the impact of implementing these software functionalities into your daily case work is going to have on your lab's operations, let's say, in the next five years?

L.R.: It's critical. So, the method that we have developed for several years and have run ad hoc on casework and found very interesting detections and novel drugs. It can now be utilized in a routine everyday basis analyzing dozens of cases and samples, again every day. And we haven't been able to do that.

And in fact, it's one of the biggest limitations for most forensic toxicology labs is to be able to process that data. The acquisition of the data, and the extraction in the laboratory is relatively straightforward. And it's really the processing of that data in a manner that can keep up. And that's what we've held back to validation because we want the final processing method, to be enacted while we completed the full validation of the method.

And we are starting to see really great results because of that. As it relates to casework, we're expecting now to be able to routinely target and process 900 components or drugs and metabolites on every single case that we see. And then the second phase of that will be to look at a non-targeted processing approach and maybe some suspect screening or other types of identification of drugs that aren't in our library. And they are the two phases that we think are required. And so, we're expecting to see a lot more things that we might not have seen in previous times and hoping that the software that's been developed in the new versions of SCIEX OS can also benefit other laboratories.

P.N.: That's very exciting. I must say, out of all our customers and collaborators, you are definitely pushing the envelope when it comes to leveraging software. So, it's really fascinating to see where you're taking your lab's operations.  I cannot wait to hear more about this ongoing work with SCIEX OS and its impact on your lab's operations in the future.

And that's a wrap for this episode on the use of software functionalities to streamline toxicology, data processing and reporting. Thank you to my guest, Luke. Thank you so much for sharing your journey with us and all the insightful conversation.

L.R.: Pleasure. Thank you for having me.

P.N.: Great. Thanks also to the viewers for watching. As always, make sure you visit our Forensic Applications page to learn more about how software solutions can really streamline your lab's operation. We also have good resources on our SCIEX OS product page. So, if you want to know more about some of the features and functionalities on the latest versions of SCIEX OS feel free to check out the SCIEX OS product page.

In the next episode, we will be joined by Sara Walton, who's a forensic toxicologist at the Center for Forensic Science Research and Education. We will discuss drug metabolism studies in a forensic toxicology setting and their application to authentic biological samples. So, make sure to tune in for that. Thank you so much again for tuning in. We'll see you next time.