= Emerging. More than 5 years before clinical availability.
= Expected to be clinically available in 1 to 4 years.
= Clinically available now.
MSACL 2018 EU : Grant

MSACL 2018 EU Abstract

Topic: Practical Training

Everything You Wanted to Know about Internal Standards But Were Too Afraid to Ask

Russ Grant (Presenter)
Labcorp

Presenter Bio: Vice President of Research and Development and Discipline Director for Mass Spectrometry at Laboratory Corporation of America.

Authors: Russell P Grant
LabCorp

Short Abstract

This one hour teaching session regarding Internal Standards will be delivered in three 20 minute vignettes.
The first session 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).

Long Abstract

Introduction

Internal standards are ideally a perfect mimic for analytes and correct for a multitude of analytical variance and bias, when designed and used correctly. Internal standards provide qualitative details that can elucidate confidence in results release apriori, such as enabling analyte peak selection (retention time) and expected peak shape (asymmetry). Internal standards are used quantitatively to correct for inter-sample recovery variance (absolute recovery and matrix effects), as such, much credence is afforded to their performance. In our experience over >15 years, many confounding and fundamental errors in these simple premises are observed. This has led to extensive determination of absolute agreement between analytes and internal standards, with some rather surprising outcomes.

Methods

Key experimental considerations and "cause-effect" will be detailed to establish when internal standards are behaving in a manner consistent with the analyte.

Session 1 will include: What level should I add IS at? what does the IS actually do? Qualitative details and error observations, quantitative assessment of binding equivalency (Reverse admixing - and when it can be misleading), drift over time using dynamic extraction and automation tools (and how to both elucidate and correct).

Session 2 will highlight examples of internal standardization failures such as the impact of excessive labeling, Isotopic contribution (from and to analyte), and when to use an "analog" internal standard - correctly.

Session 3 will detail expanded uses of Internal standards such as in-vitro redox correction (prior to receipt in the laboratory for sample analysis), results reporting outside the calibration range and how an internal standard can be used as a calibration system (and when not to!)

Results

The end result in each of these examples is an LC-MS/MS assay that is appropriate for use in patient management - in every scenario.

Conclusions & Discussion

You will take home a number of key developmental tools and practical solutions to get the most out of your Internal Standards and know when and hopefully how to correct implicit errors in their use to provide high quality clinically actionable results using LC-MS/MS


References & Acknowledgements:

I would like to acknowledge the fantastic scientists that I have had the pleasure of working with in my team over the many years in clinical diagnostics, in particular, their incredible efforts to validate and prove that quality and scientific rigor means something


Financial Disclosure

DescriptionY/NSource
Grantsno
SalaryyesLaboratory Corporation of America
Board Memberno
Stockyes Laboratory Corporation of America
ExpensesyesMSACL for Teaching

IP Royalty: no

Planning to mention or discuss specific products or technology of the company(ies) listed above:

no