Mike Wright is a Director in the Bioanalysis, Immunogenicity & Biomarker group within GSK. His team work on the development of assays for the monitoring of drugs and biomarkers, as drug development tools, in a wide variety of matrices. Prior to working at GSK, Mike worked in clinical diagnostics developing LC-MS/MS services for health trusts in the UK and Australia. Mike teaches on LC-MS/MS applications, considerations and troubleshooting and has contributed to a number of online training programs.

I'm an Associate Principal Scientist in Bioanalysis with almost 10 years experience in the development, validation and sample analysis of exogenous drugs, endogenous molecules and biomarkers with LC-MS/MS assays. I work primarily with small molecules, with some experience in peptide LC-MS/MS.

Laura Owen is a Consultant Clinical Scientist at Salford Royal NHS Foundation Trust and honorary senior lecturer at the University of Manchester where she teaches chromatography and mass spectrometry at Master’s level. Laura is also proud to be the chair of the practical training committee of MSACL EU and a past member of the endocrinology committee. While working at Wythenshawe hospital and in collaboration with the Christie hospital she became interested in the limitations of immunoassay measurement especially when using it in the breast cancer population. Laura developed and implemented the UK’s first LC-MS/MS assay for oestradiol in an NHS UKAS accredited laboratory which was made available for patient care and clinical trials.

Is your laboratory under pressure to purchase an LC-tandem MS or have the instruments arrived and your team are beginning on their mass spectrometry journey? This short course is designed for attendees implementing quantitative LC-tandem MS for patient testing who have laboratory medicine experience but no mass spectrometry training - clinical bench analysts, supervisors, R&D scientists, and laboratory directors.

After starting out with a basic chemistry refresher, theoretical concepts necessary for a robust implementation of clinical mass spectrometry will be presented, however, the main focus of the course will be on practical recommendations for:

- Starting with MSMS, LC and sample extraction parameters
- Choosing internal standards, solvents, and water, making reagents and calibrators
- How to fine tune sample preparation, LC and MSMS parameters to achieve the desired assay performance
- Pre-validation stress testing and method validation
- Preventative maintenance and troubleshooting
- Maintaining quality once your new LC-MS/MS assay has gone live

Using real-world examples, recommendations will also be given on:
- LC-MS/MS system purchasing
- site preparation and installation (dos and don’ts)
- establishing data analysis & review criteria and an interface to the LIS

The course will be a steady mixture of lectures, tutorials and problem solving sessions with our goal being to present just enough theory so you can report high quality results, while opening a window to the depth and complexity of clinical mass spectrometry such that your appetite is whetted to learn more.

Previous exposure to the principles of clinical method validation, either theoretical or practical, is assumed.

Robin Kemperman received his Bachelor's in chemistry from the HAN University of Applied Sciences in The Netherlands. Thereafter, he fulfilled his MSc and PhD in analytical chemistry at the University of Florida under the direction of Dr. Richard Yost. Currently, he works at the Children's Hospital of Philadelphia as Sr. Mass Spectrometrist in the Metabolic and Advanced Diagnostics Lab. Dr. Kemperman's work has covered a variety of aspects in mass spectrometry, including targeted analysis of steroids and ketone bodies using LC-MS/MS, bile acid, opioid, and glycan isomer separations using ion mobility spectrometry, and metabolomics High-Resolution MS. Dr. Kemperman is experienced in clinical MS-based validations and has presented his work at a variety of national and international meetings. Focusing on the future, he is interested in working on novel innovations for biomedical and clinical applications.

Inherited mitochondrial diseases can lead to disruptions in energy metabolism and abnormalities in the mitochondrial redox state because of impaired oxidation of NADH, the main reducing equivalent in the cell. As a result, the NADH/NAD+ ratio becomes elevated, which causes widespread secondary metabolic abnormalities in NAD+ utilizing pathways. Measuring the NADH/NAD+ ratio directly can be challenging due to its instability. However, there is a direct proportionality between the intramitochondrial NADH/NAD+ ratio and the ratio of the physiologic ketone bodies beta-hydroxybutyrate (BHB) and acetoacetate (AcAc). Therefore, assessing the ketone body ratio offers a more stable approach to estimate the mitochondrial redox state.

Measurement of the ketone body ratio is analytically challenging due to the instability of AcAc and the presence of BHB structural isomers like alpha-hydroxybutyrate (AHB), gamma-hydroxybutyrate (GHB), and beta-hydroxyisobutyrate (BHIB). Therefore, there was no clinically validated assay available to measure BHB, AcAc, and their ratio as a single test. Existing assays typically quantify AcAc and BHB separately using methods such as spectrophotometry, enzymology, or indirect measurements through gas chromatography. However, these methods often result in reduced accuracy of the ratio and require larger specimen quantities.

To enhance clinical care, a new rapid LC-MS/MS-based multiplex ketone body panel has been developed and clinically validated. This innovative panel only requires 10 µL of serum or plasma. In this presentation, we will provide an overview of mitochondrial diseases, including the involved pathways and currently available diagnostic tools. Additionally, we will delve into the development of the novel LC-MS/MS ketone body panel, discussing its robustness and sensitivity, along with details of the clinical validation process. Finally, we will share insights into the relationships between samples from patients with mitochondrial disorders and the outcomes obtained from the ketone body panel.

Grace discovered her love for clinical mass spectrometry when she began working at St Paul's Hospital in Vancouver in the special chemistry mass spec group with Dr. Dan Holmes in late 2010. Grace was challenged in this role but gained a wealth of knowledge and experience over her 10+ years in the SPH laboratory. She puts this experience and knowledge into use in her current role as Lab Scientist in the Newborn Screening and Biochemical Genetics lab at Alberta Precision Laboratories in Edmonton. Grace loves developing streamlined, easy to use (if possible!) clinical mass spectrometry assays; teaching others and helping others succeed; and troubleshooting (especially when the problem is solved!).

Deborah French Ph.D., DABCC (CC, TC) is currently Assistant Director of Chemistry and Director of Mass Spectrometry at the University of California San Francisco Clinical Laboratories. Her work currently focuses on the development and validation of LC-MS/MS assays for small molecules, specifically therapeutic drug monitoring, steroid hormones and toxicology. Deborah received her Ph.D. in biochemistry from the University of Strathclyde in Glasgow, Scotland and then completed a postdoctoral fellowship at St. Jude Children’s Research Hospital in Memphis, TN. She subsequently completed a ComACC Clinical Chemistry postdoctoral fellowship under the direction of Dr Alan Wu at the University of California San Francisco and is now board certified in Clinical Chemistry and Toxicological Chemistry by the American Board of Clinical Chemistry.

Jacqueline Hubbard received her BS degree in Biochemistry from the University of Vermont. She then earned her MS and PhD in Biochemistry and Molecular Biology from the University of California, Riverside (UCR). Following a one year postdoc at UCR, Dr. Hubbard completed a Fellowship in Clinical Chemistry at the University of California, San Diego Health. She is board certified in Clinical Chemistry by the American Board of Clinical Chemistry. In 2019, she took a position as an Assistant Professor in the Department of Pathology and Laboratory Medicine at the Geisel School of Medicine at Dartmouth and as the Assistant Director of Clinical Chemistry at Dartmouth-Hitchcock Medical Center. There, she focused on developing and validating drugs of abuse assays and SARS-CoV-2 serology testing. In 2022, she became the Laboratory Director at Three Rivers Diagnostics, a reference laboratory in Pittsburgh, PA. Her research focus still includes mass spectrometry method development and toxicology test interpretation.

Lorin Bachmann joined the VCU Department of Pathology in 2007. She currently serves as Co-Director of Clinical Chemistry, Co-Director of Point-of-Care Testing, Director of the New Kent Emergency Department Laboratory, Technical Advisor for the Operating Room Laboratory, Pathology Outreach and Clinical Trials, and Laboratory Director for multiple VCUHS outreach laboratories. Dr. Bachmann received her PhD in Molecular Medicine from the University of Virginia, followed by a fellowship in clinical chemistry and proteomics research at the University of Virginia. Dr. Bachmann is certified by the American Board of Clinical Chemistry.

Dr. Bachmann is active within the American Association for Clinical Chemistry (AACC), where she serves on the Board of Directors. She also serves as the Chair of the Chemistry and Toxicology Expert Panel for the Clinical Laboratory and Standards Institute (CLSI).

Dr. Bachmann’s research interests include evaluation and validation of new clinical laboratory assays, clinical laboratory analyzer design, development of mass spectrometry-based assays for the clinical laboratory and standardization of laboratory testing. She serves as the Chair of the National Kidney Disease Education Program (NKDEP)/International Federation of Clinical Chemistry Laboratory (IFCC) Joint Lab Working Group, whose goal is to accomplish standardization of urine albumin methods to enable utility of clinical decision thresholds.

Dr. Bachmann has received numerous awards for her contributions to professional societies, education and research. She serves as principal investigator for multiple industry-sponsored studies.

This is a VIRTUAL 4-Day Course with 16 total contact hours. CE to be provided.

There will be a pdf handout of the course slides provided via google classroom for registrant's use only.

Online Format

This is a virtual version of the short course that has been presented at MSACL. This online course includes 2.5-5 hours of live lecture each day for four days. Using Zoom (live online lectures, breakout rooms for interactive sessions) and Google Classroom (forms and job aids for download, on demand short lecture videos) provides additional opportunities for interactive and self-paced learning, both during the four-day course and beyond.

The resources posted in Google Classroom will be available to registrants for at least 3 months. We can’t give you hands-on experience with cutting PEEK tubing or changing check valves in an online course. But the potential with a virtual platform for networking and updates with actionable information to help you with your daily LC-MS/MS clinical practice seems almost limitless.

Course Content Description

Is your laboratory under pressure to purchase an LC-tandem MS or is the ROI you wrote last year haunting you now? This short course is designed for attendees implementing quantitative LC-tandem MS for patient testing who have laboratory medicine experience but no mass spectrometry training - CLS bench analysts, supervisors, R&D scientists, and laboratory directors. Theoretical concepts necessary for a robust implementation of clinical mass spectrometry will be presented – but the emphasis is on practical recommendations for:

1. LC-MS/MS system purchasing
2. site preparation and installation
3. defining preliminary MSMS and LC parameters for your first method
4. selecting and optimizing sample preparation for your first method
5. choosing internal standards, solvents, and water, making reagents and calibrators
6. adjusting sample preparation, LC and MSMS parameters to achieve the desired assay performance
7. establishing data analysis & batch review criteria
8. pre-validation stress testing and method validation
9. preventative maintenance and troubleshooting
10. maintaining quality in production.

Our goal is to present just enough theory so you can report high quality results, while opening a window to the depth and complexity of clinical mass spectrometry such that your appetite is whetted to learn more. The IFCC Committee for Distance Learning published a curriculum guideline for post-graduate trainees in laboratory medicine in 2017. This course includes all of the IFCC mass spectrometry curriculum listed in the “Principles of Analysis X-MS” section, except that we focus only on triple quadrupole mass spectrometry; metabolomics, proteomics and inborn errors of metabolism are not discussed. See also this reference by one of the team of short course instructors “Liquid chromatography-mass spectrometry education for clinical laboratory scientists”.

Previous exposure to the principles of clinical method validation, either didactic or practical, is assumed.