Location: Bonsai

Melissa Budelier, PhD TriCore Reference Laboratories Dr. Budelier the Medical Director of Clinical Chemistry and Toxicology at TriCore Reference Laboratories and Clinical Assistant Professor of Pathology at the University of New Mexico. Her research interests are broadly focused on developing clinically useful, mass spectrometry-based assays to improve diagnosis and treatment of human disease. Her expertise are in Toxicology/TDM, assay development and validation, and protein quantification.

Benjamin Beppler TriCore Reference Laboratories

Objectives

- Identify common challenges with reflexive urine drug screening
- Discuss the utility of 'hybrid' testing and direct to definitive testing using mass spectrometry
- Address the importance of drug panel test selection, and the potential issues with specific drug classes
- Describe the value of providing interpretive reports for urine drug testing, particularly for pain management clients

Workshop Summary

Many clinical laboratories continue to utilize a traditional urine drug testing algorithm involving an initial screen, typically via an automated immunoassay, followed by confirmation of positive and/or unexpected results using mass spectrometry. This algorithm emerged in the 1970s and 1980s from the desire to test for the use of illicit substances in the military and other workplaces. It was designed to answer the question: Are employees upholding a drug-free workplace? This algorithm presents significant limitations in many clinical situations, particularly in the areas of pain management and substance use disorder treatments, where the primary question changes to: Is my patient taking their medication as prescribed? This workshop will discuss several alternatives for urine drug testing, such as direct to mass spectrometry testing and 'hybrid' panels. It will also discuss considerations for selecting the appropriate analytes for urine drug testing panels and potential pitfalls associated with certain classes of drugs. Finally, it will introduce our recent efforts to implement the use of interpretive reporting for pain management clients.

Location: De Anza 1

	Robert Gurke, PhD Fraunhofer Institute for Translational Medicine and Pharmacology ITMP Robert Gurke received his diploma in chemistry at the Humboldt-University zu Berlin, Germany in 2012 followed by his doctoral thesis at the Technische Universität Dresden in 2016. After a short period as study director in a GLP-compliant bioanalytical company in Berlin he started working as research associate at the Institute of Clinical Pharmacology as well as the Fraunhofer ITMP in Frankfurt under the guidance of Prof. Geisslinger. Robert Gurke is head of the LC-MS analytics group in both institutions since 2021. Mr Gurke is performing LC-MS/MS analysis since starting his doctoral thesis and gained broad experience in the field of developing and validating methods for the determination of exogenous and endogenous small molecules in different complex matrices.
	Bo Burla, PhD Sling @ National University of Singapore I studied biology at the University of Zurich, Switzerland, and made my PhD in Molecular Plant Physiology in the lab of Prof. Enrico Martinoia, focusing on ABC transporters and comparative molecular phylogenetics. Subsequently, I became as researcher at the University Hospital of Zurich, where I was involved in establishing an LC/MS-based assay for the peptide hormone hepcidin and in projects studying Fabry Disease mechanisms. Biological processes, bioanalysis, clinical applications and the use of informatics to improve workflows have been my constant research interests. With this background I am now working as a senior researcher at the Singapore Lipidomics Incubator (SLING), heading our new data team that is focusing on developing workflows and software pipelines for the analytical data processing, QA/AC and exploration of the diverse lipidomics datasets generated by our lab.
	Margret Thorsteinsdottir, PhD University of Iceland Professor in Pharmaceutical Analytical Chemistry at the Faculty of Pharmaceutical Sciences, University of Iceland and R&D Director of ArcticMass LTd, Reykjavik, Iceland. Dr. Thorsteinsdóttir received her PhD from Uppsala University, Sweden in 1998. From 2000 to 2009 she was the managing director of Bioanalytical Laboratories at deCODE Genetics, Reykjavik, Iceland. She has extensive experience in development of analytical methods for metabolite profiling and quantification of clinical biomarkers in various biofluids utilizing chemometrics with the goal of improved clinical management of patients towards personalized patient care. Her current research interest includes studies of lipid metabolism in cancer cells and profiling plasma derived biomarkers for early detection of BRCA-related breast cancer. She is responsible for implementation of clinical mass spectrometry for support of diagnostics and therapeutic drug monitoring in collaboration with ArcticMass and the Landspitali University Hospital, Reykjavik, Iceland with major focus on quantitative targeted proteomics for clinical diagnosis. She is a principal investigator of the Icelandic Research Rannis projects, profiling metabolites for breast cancer diagnosis and search for novel biomarkers for early breast cancer diagnosis by metabolomics. Dr. Thorsteinsdóttir is a principal investigator for the Marine Biotechnology ERA-net project CYNOBESITY and the Horizon 2020 project MossTech, with the main task to isolate, identify and structurally characterize bioactive compounds from cyanobacteria, Icelandic mosses and liverworts. She is one of the founders of Females in Mass Spectrometry (FeMS), she is a vice-leader of the working group clinical significance and applications of (epi)lipidomics in the pan-European network, EpiLipidNET and vice-chair of the Nordic Metabolomics Society.
	Anne K. Bendt, PhD Singapore Lipidomics Incubator (SLING), National University of Singapore Anne K Bendt studied Biology focusing on marine biotechnology (Greifswald University, Germany), followed by a PhD in Biochemistry (Cologne University, Germany) employing proteomics and transcriptomics. Driven by her fascination for infectious diseases, she joined the National University of Singapore (NUS) in 2004 to develop lipidomics tools for tuberculosis studies. She is now a Principal Investigator at the Life Sciences Institute, NUS, focussing on translation of mass spec technologies into clinical applications, and serving as the Deputy Director of the Singapore Lipidomics Incubator (SLING) taking care of operations and commercialization.

Objectives

It is the objective of the workshop to provide an introduction into pre-analytical considerations for clinical application of MS-based analytics, with a special focus on lipids. However, these considerations are in many cases independent of specific analytes of interest and can hence be applied for polar metabolites as well as proteins. The workshop is focused on main hurdles to be considered when performing clinical research using LC-MS based determination of lipids namely: (I) pre-analytical sample handling, (II) frequent generation of patient samples as well as (III) overall cohort and study design.

Summary

Lipids are involved in a broad spectrum of functionalities in the organism and implicated in a variety of physiological and pathological processes. Changes in lipid levels are promising biomarkers for early diagnosis, prognosis of disease progression, or guidance for selecting promising therapeutic approaches. However, biomarker discovery in the field of lipidomics is a very challenging process since lipids require specific procedures regarding sampling (including selection of sample type and collection procedures, storage conditions and number of freeze-thaw cycles), sample preparation and analysis for reliable determination. As especially pre-analytical sample handling is a critical step for the reliable analysis of the lipidome, a close cooperation with the clinicians is necessary. This ensures following a highly standardized protocol for venous blood sampling to avoid several pre-analytical pitfalls potentially changing the lipid profile ex vivo. As collecting venous blood samples is very laborious for patients as well as clinicians, other ways for a more frequent sample collection are necessary. Therefore, capillary blood sampling using microsampling devices is an auspicious way to complement the strategy of analyzing venous blood-based samples taken in the clinics. Besides considering the right sampling strategy, the structured recording of sampling details and subject metadata, the overall planning of the study and also the cohorts to be included is of high relevance. All mentioned points have to be considered before starting a clinical research project applying lipidomics to generate high quality data making biomarker discovery possible.

Syllabus
- Pre-Analytical factors influencing lipid concentrations
- Capillary vs. venous blood sampling - the potential of microsampling
- Cohort & Study design for lipidomics in clinical research

Location: De Anza 3

Cory Bystrom, PhD Ultragenyx

Russell Grant, PhD Labcorp Dr. Grant earned a first-class honors degree in Industrial Chemistry from Cardiff University and a PhD in Chromatographic and Mass Spectrometric technologies from the University of Swansea, Wales, United Kingdom. He continued his scientific training in various industrial settings, which have included senior scientist at GSK, Principal scientist at Cohesive Technologies, Technical director at Eli Lilly, and Director of Mass Spectrometry at Esoterix Endocrinology. Dr Grant is currently the Vice President of Research and Development and co-discipline director for Mass spectrometry at Labcorp. Dr Grant has pioneered the use of direct injection technologies, chromatographic systems multiplexing, microsampling, utility of automation, and other new analytical platforms in direct patient care. His research goals are focused upon improvements in speed, sensitivity, and quality of liquid chromatography with tandem mass spectrometric (LC-MS/MS) analytical systems and assays. Dr Grant has been awarded 100 patents and received both the MSACL Distinguished contribution award and ASMS AL Yergey “Unsung Hero” Award in 2024 for his contributions to Clinical Diagnostics using Mass Spectrometry.

* with Special Guest Stars *

Objective:
Workshop attendees will gain an understanding of the clinical assay development framework for proteins and peptides established in CLSI C64. Using C64 as a framework for development will help the laboratorian approach protein and peptide assay development confident that analytical performance will meet clinical requirements.

Summary:
The development and validation of quantitative assays for proteins and peptides for clinical use is a significant undertaking and presents challenges that are distinct from small molecules. The heterogeneous nature of proteins and the frequent requirement to use proteolysis aided workflows add complexity that require careful attention to definition The workshop will be an interactive discussion covering each chapter in C64, guided by authors that contributed extensively to the development of the document.

Objective 1: Understand the holistic process of delivering a clinically relevant LC-MS/MS protein/peptide assay from inception to validation.

Objective 2: Recognize the factors in assay development that are unique to proteins and peptides in comparison to traditional small molecule assays.

Objective 3: Understand key experimental requirements for successful development and validation.

Syllabus:
1. Introduction to C64, philosophy and scope
2. Interactive discussion of each chapter