A Review of LCMS

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Vol. 25 No. 11 Page 39

This versatile analytical chemistry technique has exciting potential for growth.

The coupling of mass spectrometry and liquid chromatographic techniques results in a cutting-edge analytical chemistry technique known as liquid chromatography mass spectrometry (LCMS). The qualitative and quantitative capabilities of LCMS make it useful for various applications, including testing for newborn errors of metabolism, drugs of abuse, pain management, clinical and forensic toxicology, endocrinology, therapeutic drug monitoring, and, currently, microbiology. However, the list of applications continues to grow as the field develops rapidly.

In a recent interview with ADVANCE, Y. Victoria Zhang, PhD, director of the Clinical Mass Spectrometry and Toxicology lab at the University of Rochester Medical Center, and chair of the American Association of Clinical Chemistry (AACC) Mass Spectrometry and Separation Sciences Division, discussed the various benefits and limitations of this technology and the many exciting trends in this field for the near future.

Advantages

According to Zhang, a major strength of LCMS is its specificity. “Applications of LCMS have benefited from its high specificity, which is due to multiple criteria used for compound identification—including high performance liquid chromatography (HPLC) retention time, compound molecular weight and fragmentation features (multiple reaction monitoring process),” Zhang said. Due to its specificity, LCMS allows lab scientists to analyze a much wider range of individual compounds that cannot be separated by using an immunoassay.

For many tests, LCMS also provides high sensitivity because it has the ability to detect low levels of analytes. Traditionally, immunoassays have been used to measure low molecular weight compounds. However, LCMS has proven to be more sensitive than immunoassays in such cases as testosterone and thyroglobulin testing, due to the fact that LCMS is less affected by endogenous interferences. This factor allows LCMS to detect lower concentrations of an analyte of interest with a higher level of certainty.

Another benefit that is unique to LCMS is the short development time, owing to its ability to detect compounds that do not have suitable antibodies. For example, LCMS provides great benefits for monitoring immunosuppressant drugs, due to the limitations on suitable antibodies. In this case, unlike an immunoassay, mass spectrometry does not require antibodies, which take a significant amount of time and effort to develop and take even longer to screen.

Volume Justifies Need

Despite its many advantages, LCMS is not without limitations. Due to its complexity, LCMS requires a high level of training and experience in lab staff to operate the instruments properly. Nearly all LCMS assays are laboratory-development tests that require a deep understanding of the technology and regulatory requirements to properly develop and validate the assays in house. This also plays a part in staffing considerations, Zhang noted.

The high capital cost of these platforms is another challenge for labs, which means that this technology is not found in every lab. “It is only when the institution has the sample volume and the needs that can justify the expense,” explained Zhang. However, the low operating cost of these machines helps counter the cost of acquiring the instrumentation.

A further limiting factor of LCMS is the lack of automation involved. “The technology itself is a very manual and labor intensive process,” said Zhang. Though the testing method itself is automated, sample preparation and data analysis remain a largely manual process.

What’s Next?

When asked if there is a potential for growth in this field, Zhang readily responded, “Yes, absolutely. That’s why I’m very excited about the field and continue to be amazed by all the potentials in this powerful platform in clinical applications.” According to Zhang, who has been working in the field for nearly 15 years, major trends in improvements are coming from several different areas.

Both the instrumentation and the accompanying software are becoming more user-friendly, especially as communication between manufacturers and users continues to improve. The instrumentation is also progressively becoming smaller, which may allow for easier transport and greater affordability.

Another development in the field is seen in the expanding range of applications for LCMS. “The field is moving very fast,” Zhang said. Traditionally, LCMS/MS has been used for the measurement of small molecules in clinical applications, but there are now applications for proteins and peptides.

Thyroglobulin is one example of using targeted mass spectrometry for protein/peptide assay in clinical applications. This significantly enhances the understanding and applications of mass spectrometry in laboratory medicine. In addition, Zhang said, this assay has overcome a long-standing challenge for immunoassay-based assays due to endogenous antibody interferences. “This provides better care for patients that have been affected by this interference,” Zhang explained.

Improvements are not only being made on the clinical pathology side—there has also been much interest on the anatomic pathology side. Tissue-imaging by mass spectrometry is one example. “We can not only analyze body fluids, but we can analyze tissue samples as well,” Zhang said.

This technology has also significantly impacted the microbiology field. “The introduction of MALDI-TOF mass spectrometry revolutionized the practice in microbiology in the past few years by significantly reducing the turnaround time for microorganism identification in comparison to traditional cell culture methodology,” explained Zhang.

As previously mentioned, there is room for growth in the automation of LCMS. “I think we are moving in the right direction but there are a lot of gaps to be filled,” Zhang said.

Lastly, the training of lab personnel is yet another area undergoing improvement. As more medical technologists, residents, and fellows are trained in this technology, the better the technology will be implemented throughout clinical labs. With that purpose in mind, Zhang is working alongside the AACC and fellow colleagues throughout academia, regulatory agencies, and professional organizations in the effort to enhance the understanding of the field.

Overall, the future is looking bright for LCMS throughout clinical labs as improvements are continuing to be made in the technology, applications, and lab staff training. Ultimately, as Zhang said, working for the advancement of this technology is for “precision medicine and the betterment of patient care.”

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Kirsten Malenke
Kirsten Malenke

Kirsten Malenke is a staff writer at ADVANCE. Contact kmalenke@advanceweb.com.

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