Mass spectrometry (MS) is disseminating rapidly in clinical laboratories but remains a technically complex method to implement and to maintain. Multiple sessions at the 69th AACC Annual Scientific Meeting & Clinical Lab Expo will offer to labs at all stages of MS development advice and guidance on different aspects of this technology. Attendees have 14 Brown Bag sessions to choose from, plus other sessions that deal with the analytical aspects of developing or operating MS methods.

In one of those sessions, From a Brick to a Fortress: Building a Solid Clinical Mass Spectrometry Method One Brick at a Time (192012), Deborah French, PhD, assistant director of chemistry and director of mass spectrometry at the University of California San Francisco will start things off by covering the basics of liquid chromatography and tandem MS (LC-MS/MS).

Session moderator Grace Van der Gugten, BSc, LC-MS/MS assay development specialist at Provincial Health Services Authority at St. Paul’s Hospital in Vancouver, Canada, will give a talk on LC-MS/MS method development and pre-validation, followed by Julianne Botelho, PhD, a research chemist at the Centers for Disease Control and Prevention, who will discuss validation and post-implementation monitoring for LC-MS/MS methods.

“The second and third presentations would be useful for labs that have MS but are still in the process of developing and validating methods. And the third presentation would be useful for labs already using MS but looking for guidance in useful parameters to monitor and what variations in these parameters could indicate,” the speakers told CLN Stat.

MS poses several implementation challenges, starting with the fact that mass spectrometers aren’t like other instrumentation commonly found in clinical labs, according to French, Van der Gugten, and Botelho.

In order to run LC-MS/MS methods, laboratories need to develop and validate methods in-house rather than use already developed tests/kits. This involves selecting calibrators, quality control materials, mobile phases, chromatography columns, and a number of other reagents and consumables. Yet clinical laboratories have become highly automated and new technologists now have limited experience with manual procedures, the speakers continued.

“There is an added complication of sample preparation, which can be quite intensive depending on the analyte(s). In order to successfully develop, validate, and implement an LC-MS/MS assay, it would be helpful to have a dedicated technologist or scientist,” the speakers recommended.

Making a plan is key for developing methods and for pre-validation and validation testing, the speakers suggested. From the very beginning, labs should determine the necessary validation experiments and establish acceptance criteria.

“If your assay is not performing well in the development or validation stage, it is only going to get worse when you go into production.  Don’t be afraid to go back to the drawing board—it is easier to make changes and re-validate before the assay is in production! Making sure you have a robust method from the start will save you a lot of pain later on,” they advised.

Another can’t miss session is MALDI-TOF Mass Spectrometry: Not Just For Clinical Microbiology Labs Anymore (33212). MALDI-TOF MS is the most revolutionary advance for organism identification seen in the last decade, Tony Hu, PhD, associate professor at the Biodesign Institute at Arizona State University’s Virginia G. Piper Center for Personalized Diagnostics, and one of the session’s speakers, told CLN Stat.

Not only is it more accurate than traditional culture-based methods, “but identifications also are produced more rapidly and at significantly lower cost,” said Hu, who plans to discuss the immuno-MALDI technique involving immuno-affinity enrichment of peptides specific to Mtb-secreted antigen, followed by MALDI-MS detection.

A desire to bring some of the MALDI-TOF MS methods for microbiology applications to the forefront—and out of the shadow of microbe-focused methods—was a motivator for this session, according to co-presenter Mari DeMarco, PhD, DABCC, FACB.

“Chemistry-focused MALDI-TOF MS applications include everything from tools for quality control of reagents intended for immunoassay or LC-MS/MS assays to development of workflows for peptide quantitation to identification of drugs of abuse. Through this session we hope to share our enthusiasm for the great potential of MALDI-TOF MS methods in clinical chemistry laboratories,” DeMarco, clinical associate professor at the University of British Columbia and a clinical chemist at St. Paul's Hospital in Vancouver, Canada, told CLN Stat.

Labs might consider MALDI-TOF over LC-MS/MS in certain situations, Hu said. “Techniques such as immuno-multiple reaction monitoring (MRM) can provide absolute quantitation of peptides and small proteins in body fluids by means of MS/MS,” he noted.

This method usually calls for sophisticated instrumentation like LC, electrospray ionization (ESI)-MS/MS or triple quadrupole MS, and highly skilled operators. MALDI-TOF MS as a detection system is much faster and technically less sophisticated than LC-ESI or triple quad MS-based systems, according to Hu. It’s also suitable for high throughput analyses. “Furthermore, many hospitals and public health laboratories routinely employ MALDI-TOF instrumentation for microbial identification. Therefore, it can be argued that MALDI may be the preferred technique and platform for MS-based clinical diagnostic assay development,” he noted.

Rounding off the session is Yusheng Zhu, PhD, a professor at Pennsylvania State University Hershey Medical Center, whose talk is on MALDI-TOF MS’ applications in molecular genetics and toxicology.

“From my presentation, participants will learn how to use MALDI-TOF MS for quantitative and qualitative analysis of genetic markers. Additionally, they will learn the application of MALDI-TOF-MS imaging in the study of chronological distribution of drugs in hair samples,” Zhu told CLN Stat.

With the Brown Bag sessions, attendees get to mingle with speakers and fellow participants in a smaller, more intimate setting. Following is a list of Brown Bags that feature MS topics: 

  • Matrix Effects in LC-MS Assays: Evaluation and Strategies to Overcome Testing Issues (42112) (52212)

  • Troubleshooting and Method Development for the Extraction and Quantification of Cannabinoids from Oral Fluid (42117) (52217)
  • MALDI-TOF Mass Spectrometry and Its Applications in Laboratory Medicine (43102) (53202)
  • Strategies for Streamlining Analytical and Post-Analytical Processes in Clinical Urine Multi-Target Drug Testing Using LC-MS/MS Technology (43124) (53224)
  • The Evolution of Next Generation Clinical Mass Spectrometry (43131) (53231)
  • Leveraging CLSI Guidelines for Validation of Mass Spectrometry Assays (43133) (53233)

  • Evaluation of MALDI-TOF Mass Spectrometry for Pharmacogenetic Testing in Clinical Laboratories (44108) (54208). 

Learn about all things MS at the 69th AACC Annual Scientific Meeting & Clinical Lab Expo in San Diego July 30–Aug. 3.