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.

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.

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.

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.

AGENDA

Day 1
Chemistry - Back to Basics
Sample Extraction
Essentials of Chromatography
Tutorial 1

Day 2
Mass Spectrometry
Tutorial 2

Day 3
Internal Standards
Reagents and Calibrators
Validation

Day 4
Vendor presentations*
Processing data and checking procedures
Maintenance, SST and Troubleshooting
Procurement and Infrastructure

*TBD

David S. Millington, PhD, is Emeritus Professor of Pediatrics, recently retired from Duke School of Medicine. He and his colleagues pioneered the application of tandem mass spectrometry for the targeted analysis of acylcarnitines that became a frontline diagnostic test for defects of fat oxidation and branched-chain amino acid catabolism. Subsequently, the method was modified to include several essential amino acids and applied to dried blood spots, paving the way for the expansion of newborn screening for from a handful to over 30 metabolic conditions. As the expanded newborn screening method has spread, Dr. Millington has developed educational material and taught many laboratorians and follow-up coordinators worldwide how to apply the technology and interpret results. Expanded newborn screening by MS/MS is now applied to tens of millions of neonates annually and has help save thousands of lives. More recently, he has collaborated with a North Carolina biotechnology company to bring digital microfluidics into biochemical diagnostics and newborn screening. He has also pioneered novel biomarker assays for numerous lysosomal storage conditions to facilitate patient diagnosis and monitoring. Dr Millington has published over 200 research articles and book chapters and has served on the North Carolina Newborn Screening Program Advisory Board since 1990. He was honored jointly with Dr Mohamed Rashed by the ISNS with the Robert Guthrie award for outstanding contributions to newborn screening in 1996. He was also honored by the MSACL in 2015 with their first Distinguished Contribution Award in recognition of achievements made in the field of clinical mass spectrometry.

A fireside chat with David Millington.

JMSACL : Open Access : How Mass Spectrometry Revolutionized Newborn Screening

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 received the MSACL Distinguished contribution award and ASMS AL Yergey “Unsung Hero” Award in 2024 for his contributions to Clinical Diagnostics using Mass Spectrometry.

The first session will be given as two 90-minute linked vignettes and will explore established and novel approaches to definitively improve analytical measurement performance - with the end goal of improving an assay LLOQ. The answer isn't necessarily buy a newer mass spectrometer, it is attention to details and maximizing each step of the process. This one-hour session will be presented in three modules. The first module, Foundations, will focus on assessment and improvements to pipetting techniques, control of adsorptive losses and use of surrogate IS studies to assess imprecision reduction during assay development. The second module, Formulation, will focus on system cleanliness, the fallacy of S:N, LC system dead-volume and flow rate implications, ionization efficiency enhancements, source and optics fouling, the value of signal summing + scheduled MRM and quadrupole resolution settings.
The third module, Finesse, will tie these concepts and practical solutions together to demonstrate their use for assays that have been developed, validated and deployed. Particular focus will be made to detailed establishment of “on-column” amount, controlling adsorptive losses throughout the assay, 2D-LC to decouple selectivity and sensitivity variables, selectivity and stoichiometry of reagents in worst case specimens, the consideration that while counter counter-intuitive, more degrees of selectivity (analyte losses) may be optimal for an assay.

Take Home Pearls:
- How to practically improve an assay performance as defined by lower levels of quantification
- How to enhance the throughput of an LC-MS/MS assay by paying attention to the little details
- How to enhance signal responses in a mass spectrometer without sacrificing quality"

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 received the MSACL Distinguished contribution award and ASMS AL Yergey “Unsung Hero” Award in 2024 for his contributions to Clinical Diagnostics using Mass Spectrometry.

Note: This is Part 2 of a two part session.
The first session will be given as two 90-minute linked vignettes and will explore established and novel approaches to definitively improve analytical measurement performance - with the end goal of improving an assay LLOQ. The answer isn't necessarily buy a newer mass spectrometer, it is attention to details and maximizing each step of the process. This one-hour session will be presented in three modules. The first module, Foundations, will focus on assessment and improvements to pipetting techniques, control of adsorptive losses and use of surrogate IS studies to assess imprecision reduction during assay development. The second module, Formulation, will focus on system cleanliness, the fallacy of S:N, LC system dead-volume and flow rate implications, ionization efficiency enhancements, source and optics fouling, the value of signal summing + scheduled MRM and quadrupole resolution settings.
The third module, Finesse, will tie these concepts and practical solutions together to demonstrate their use for assays that have been developed, validated and deployed. Particular focus will be made to detailed establishment of “on-column” amount, controlling adsorptive losses throughout the assay, 2D-LC to decouple selectivity and sensitivity variables, selectivity and stoichiometry of reagents in worst case specimens, the consideration that while counter counter-intuitive, more degrees of selectivity (analyte losses) may be optimal for an assay

Take Home Pearls:
- How to practically improve an assay performance as defined by lower levels of quantification
- How to enhance the throughput of an LC-MS/MS assay by paying attention to the little details
- How to enhance signal responses in a mass spectrometer without sacrificing quality"

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 received the MSACL Distinguished contribution award and ASMS AL Yergey “Unsung Hero” Award in 2024 for his contributions to Clinical Diagnostics using Mass Spectrometry.

One of the true killer applications in mass spectrometry involves the appropriate use of stable labelled internal standard materials to correct for a multitude of analytical variances. With great power, comes great responsibility (credit, Ben Parker in Spiderman). The second session will be given as two 90-minute linked vignettes and will explore established and novel approaches to definitively select and appropriately use internal standards, both in development and also into clinical utility, with the end goal of improving assay imprecision and error detection. The first module will describe in detail the "What, Why and How" Internal standards should be used in isotope dilution LC-MS/MS assays. The second session "But what about when?" will describe situations where Internal Standards fail criterion for use and how to correct deficiencies for effective LC-MS/MS assays. The third session will describe the "Unique capabilities" afforded to analytical measurement when used as internal calibrators/pre-analytic correction tools and in method development (as surrogates for analytes).

Take Home Pearls:
- How to rationalize and employ an internal standard in quantitative mass spectrometry
- How to use an internal standard to aid in assay development and as a troubleshooting tool
- How to creatively use stable labelled materials for quantification and historical calibration

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 received the MSACL Distinguished contribution award and ASMS AL Yergey “Unsung Hero” Award in 2024 for his contributions to Clinical Diagnostics using Mass Spectrometry.

Note: This is Part 2 of a two part session.
One of the true killer applications in mass spectrometry involves the appropriate use of stable labelled internal standard materials to correct for a multitude of analytical variances. With great power, comes great responsibility (credit, Ben Parker in Spiderman). The second session will be given as two 90-minute linked vignettes and will explore established and novel approaches to definitively select and appropriately use internal standards, both in development and also into clinical utility, with the end goal of improving assay imprecision and error detection. The first module will describe in detail the "What, Why and How" Internal standards should be used in isotope dilution LC-MS/MS assays. The second session "But what about when?" will describe situations where Internal Standards fail criterion for use and how to correct deficiencies for effective LC-MS/MS assays. The third session will describe the "Unique capabilities" afforded to analytical measurement when used as internal calibrators/pre-analytic correction tools and in method development (as surrogates for analytes).

Take Home Pearls:
- How to rationalize and employ an internal standard in quantitative mass spectrometry
- How to use an internal standard to aid in assay development and as a troubleshooting tool
- How to creatively use stable labelled materials for quantification and historical calibration

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 received the MSACL Distinguished contribution award and ASMS AL Yergey “Unsung Hero” Award in 2024 for his contributions to Clinical Diagnostics using Mass Spectrometry.

Central to determining assay quality and results reporting apriori is the fundamental belief that one is selectively measuring the analyte of choice. The use of transition ratio monitoring, while somewhat known to many users of tandem mass spectrometry, still provides a multitude of discreet challenges in the development, use and interrogation of chromatographic data. Historical rules based review, driven by qualifier transition yield relative to the quantifier transition fails to provide the appropriate quality considerations based on meaningful data. This pair of 90 minute presentations will include an arc of developmental understanding, from initial assessments (including favoring selectivity over sensitivity), validation of ion ratio's (sample types and concentrations) and use of transition ratio's (multi-level, non-symmetrical and statistically based).

Take home "Pearls" include:
1. How to select appropriate transitions for use in transition ratio monitoring - including tools to enhance response function for low intensity transitions
2. How to improve the precision of Transition ratio's through scheduling and appropriate dwell times
3. How to design transition ratio tolerances to enhance medical utility and including when to ignore the qualifier transition

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 received the MSACL Distinguished contribution award and ASMS AL Yergey “Unsung Hero” Award in 2024 for his contributions to Clinical Diagnostics using Mass Spectrometry.

Note: This is Part 2 of a two part session.
Central to determining assay quality and results reporting apriori is the fundamental belief that one is selectively measuring the analyte of choice. The use of transition ratio monitoring, while somewhat known to many users of tandem mass spectrometry, still provides a multitude of discreet challenges in the development, use and interrogation of chromatographic data. Historical rules based review, driven by qualifier transition yield relative to the quantifier transition fails to provide the appropriate quality considerations based on meaningful data. This pair of 90 minute presentations will include an arc of developmental understanding, from initial assessments (including favoring selectivity over sensitivity), validation of ion ratio's (sample types and concentrations) and use of transition ratio's (multi-level, non-symmetrical and statistically based).

Take home "Pearls" include:
1. How to select appropriate transitions for use in transition ratio monitoring - including tools to enhance response function for low intensity transitions
2. How to improve the precision of Transition ratio's through scheduling and appropriate dwell times
3. How to design transition ratio tolerances to enhance medical utility and including when to ignore the qualifier transition

By the end of this 3-hour workshop, participants will be able to:

Understand ISO 15189 Requirements: Clearly articulate the key requirements and standards of ISO 15189 specific to metabolomic labs, including documentation, quality control, and management responsibilities.

Implement Best Practices: Apply best practices and strategies for establishing a quality management system (QMS) that meets ISO 15189 standards, including risk management, external and internal quality control, corrective actions, and continual improvement processes.

Prepare for Certification: Develop a step-by-step plan to prepare their metabolomic lab for ISO 15189 certification, including conducting internal audits, addressing non-conformities, and engaging with accrediting bodies.

Utilize Tools and Resources: Identify and utilize tools, resources, and software solutions that can aid in meeting ISO 15189 requirements, enhancing lab efficiency, and ensuring compliance.

Troubleshoot Common Challenges: Recognize and troubleshoot common challenges and obstacles faced during the ISO 15189 certification process, with special emphasis on developing a proper method validation protocol and implementing an effective training and competency program. Gain practical guidelines and solutions to overcome these issues.