Zlatuse Clark (Presenter)
ARUP Laboratories
Bio: B.S. in analytical chemistry from Masaryk University, Brno, Czech Republic Ph.D. in bioanalytical chemistry from Brigham Young University, Provo, Utah Currently an R&D scientist at ARUP Laboratories, Salt Lake City, Utah
Authorship: Zlatuse D Clark
ARUP Laboratories, Salt Lake City, UT
| Short Abstract The popularity of LC-MS/MS-based methods for clinical testing continues to rise. However, despite their superior analytical specificity, these methods may still suffer from interference affecting method accuracy and precision, and hence negatively impacting patient care. Examples of interference issues in various methods and how they were resolved will be shown throughout the entire session. This session segment will discuss: • Sources of guidelines for interference testing in method development/validation and routine testing (CLSI, CAP, SWGTOX) • What is analytical interference and where does it come from? • How do we define acceptable interference levels? |
Long Abstract
Introduction
The popularity of LC-MS/MS-based methods for clinical testing continues to rise. However, despite their superior analytical specificity, these methods may still suffer from interference affecting method accuracy and precision, and hence negatively impacting patient care. The aim of this Practical Training Track presentation is to introduce the participant to what analytical interference is, where it may come from, how we test for it in LC-MS/MS, ways to mitigate it, and how to monitor for it (1). Practical examples of interference issues and how they were resolved will be shown.
Methods
Format not applicable to this presentation.
Results
What are the different sources of guidelines for interference testing?
CLSI, CAP, SWGTOX and other regulatory documents will be discussed.
What is analytical interference and where does it come from?
Analytical interference is the effect of a substance, identified or not, that causes the measured concentration of an analyte to differ from its true value (2). Interfering substances may come from many different sources and may be introduced at any time before or during the testing workflow. Examples include: compounds related to patient treatment (drugs, parenteral nutrition, plasma expanders); metabolites produced in pathological conditions, substances ingested by patients (alcohol, drugs of abuse, nutritional supplements, food), substances added during sample preparation (anticoagulants, preservatives, stabilizers); contamination during sample handling (hand cream, serum separators, collection tube stoppers, leachables from plastic consumables); and interferences arising from the sample matrix itself, such as hemolysis, icterus, and lipemia (3).
How do we define acceptable interference levels?
When defining acceptable interference levels labs need to consider the clinical context in which a test result will be used as well as the allowable analytical error limits.
Conclusions & Discussion
After this segment attendees should be able to:
1. List sources of guidelines for interference testing
2. Define analytical interference and identify its various sources
References & Acknowledgements:
References
1. Clark ZD, Balloch S, Calton L, Mason D. Interference Testing and Mitigation in LC-MS/MS Assays. Clinical Laboratory News 2017;43(8):22-5.
2. CLSI. Evaluation of matrix effects; Approved guideline – second edition. CLSI document EP14-A2.Wayne (PA): CLSI; 2005.
3. CLSI. Interference testing in clinical chemistry; Approved guideline – second edition. CLSI document EP7-A2.Wayne (PA): CLSI; 2005.
4. Clark ZD, Cutler JM, Pavlov IY, et al. Simple dilute-and-shoot method for urinary vanillylmandelic acid and homovanillic acid by liquid chromatography tandem mass spectrometry. Clin Chim Acta 2017;468:201–8.
5. Clark ZD, Cutler JM, Frank EL. Practical LC-MS/MS method for 5-hydroxyindoleacetic acid in urine. J Appl Lab Med 2017;1:387–99.
6. Matuszewski BK, Constanzer ML, Chavez-Eng CM. Strategies for the assessment of matrix effect in quantitative bioanalytical methods based on HPLC-MS/MS. Anal Chem 2003;75:3019–30.
7. Annesley TM. Ion suppression in mass spectrometry. Clin Chem 2003;49:1041–4.
8. Bonfiglio R, King RC, Olah TV, et al. The effects of sample preparation methods on the variability of the electrospray ionization response for model drug compounds. Rapid Commun Mass Spectrom 1999;13:1175–85.
9. King R, Bonfiglio R, Fernandez-Metzler C, et al. Mechanistic investigation of ionization suppression in electrospray ionization. J Am Soc Mass Spectrom 2000;11:942–50.
10. Clark ZD, Strathmann FG, McMillin GA. Diluting and shooting yourself in the foot: Complications with sample-to-sample variations in signal suppression. MSACL 2013 podium presentation.
11. CLSI. Liquid chromatography-mass spectrometry methods; Approved guideline. CLSI document C62-A. Wayne (PA): CLSI; 2014.
12. Lynch KL. LC-MS/MS quality assurance in production: The real work begins after validation. Clinical Laboratory News 2017;43(5):28–9.
13. Zabell APR, Stone J, Julian RK. Using big data for LC-MS/MS quality analysis. Clinical Laboratory News 2017;43(5):30–1.
Acknowledgements
Much gratitude to Dr. Frederick Strathmann for collaboration on several projects addressing the various aspects of interference testing and for facilitating exciting opportunities to present and publish on these topics. Many thanks as well to Donald Mason, Lisa Calton, and Stephen Balloch for their contributions as coauthors of our recent Clinical Laboratory News article “Interference Testing and Mitigation in LC-MS/MS Assays,” which was used in preparing this presentation.
The work presented here was supported in part by ARUP Institute for Clinical and Experimental Pathology®.
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