Judy Stone, MT (ASCP), PhD, DABCC has worked with LC-MS in diagnostic laboratories since 1999. Her clinical practice involved small molecule method development, instrument to instrument and instrument to LIS interfacing, LC-MS automation, monitoring quality of LC-MS methods in production and staff training for clinical LC-MSMS. She served as faculty chair for the 2009 AACC online certificate program “Using Mass Spectrometry in the Clinical Laboratory”, as a scientific committee member for the MSACL Practical Training track, and was editor-in-chief for the AACC Clinical Laboratory News quarterly feature series on Clinical LC-MS. She enjoys documenting and presenting esoteric as well as absurdly common LC-MS problems in creative ways in order to help trainees learn troubleshooting (and avoid repeating her mistakes).

The U.S. FDA Final Rule (6 May 2024) on Laboratory Developed Tests (LDT) is a concern for all CLIA laboratories performing LC-MSMS testing for patient care. The ACLA and AMP lawsuits, and Supreme Court “Chevron” ruling, have added uncertainty to the future for the Final Rule. But the first compliance deadline of 6 May, 2025, required for all LDTs, is on the horizon. Expert overviews of the LDT Final Rule are now available (recorded webinars) and more are planned by the FDA, ADLM, CLSI, and CAP. After 6 May 2024, MSACL formed a Compliance and Accreditation Committee (CAC). A primary committee goal is to support clinical LC-MSMS users who are planning their compliance with the U.S. FDA LDT Final Rule.

MSACL Connect, with MSACL-CAC Co-chairs Jacqueline Hubbard and Judith Stone, will present a webinar focusing specifically on in depth review and translation of regulatory to clinical laboratory language for the Complaints, Medical Device Reporting (MDR), Corrections and Removals requirements of LDT Final Rule compliance. These are the sections of the FDA’s four-year enforcement discretion phaseout that are due by 6 May 2025. Recommendations for an action plan and templates of SOPs/Forms/Logs designed to help laboratories customize their compliance for these requirements will be discussed. The document templates will be available for download to webinar attendees.

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.

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 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.

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 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.

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 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.

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.