LC-MS/MS in the Clinical Laboratory - Where to From Here?
Stefan Kg Grebe1, Ravinder J Singh
1Departments of Laboratory Medicine & Pathology and Medicine.
The Clinical Biochemist. Reviews
|April 1, 2011
Summary
Liquid chromatography-tandem mass spectrometry (LC-MS/MS) offers superior specificity and growing applications in clinical labs, particularly for endocrine testing. Future growth is expected in peptide and protein analysis, building on its success with small molecules.
Area of Science:
- Clinical chemistry
- Analytical chemistry
- Biochemistry
Background:
- Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has rapidly grown in clinical laboratories over the past 10-15 years.
- It provides superior analytical specificity compared to immunoassays and conventional HPLC for low molecular weight analytes.
- Initially prominent in drug/toxicology and newborn screening, LC-MS/MS use has been largely adopted by endocrine laboratories.
Purpose of the Study:
- To review the growth, advantages, and limitations of LC-MS/MS in clinical laboratories.
- To highlight key applications in endocrine testing and discuss strategies for improving throughput, sensitivity, and specificity.
- To explore the emerging role of LC-MS/MS in peptide and protein analysis.
Main Methods:
- Review of LC-MS/MS applications and advancements in clinical diagnostics.
- Discussion of techniques to enhance throughput, such as direct sample injection and multiplexing.
- Analysis of methods to improve specificity and sensitivity, including sample cleanup and chromatographic optimization.
Main Results:
- LC-MS/MS is now standard for many steroid and biogenic amine assays in US reference laboratories, with increasing adoption in smaller labs.
- Assays for mineralocorticoids, glucocorticoids, sex steroids, metanephrines, and 25-hydroxy vitamin D demonstrate LC-MS/MS advantages.
- While throughput lags behind immunoassays, ongoing technological improvements address limitations in sensitivity, specificity, and throughput.
Conclusions:
- LC-MS/MS has become a cornerstone of modern clinical diagnostics for small molecules, especially in endocrinology.
- The technology is poised for significant expansion into peptide and protein analysis, mirroring its success in low molecular weight applications.
- Targeted peptide and protein testing using LC-MS/MS is proving effective for answering specific clinical and analytical questions.
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