Making patient impact with ions: A conversation on the value of mass spectrometry

Although mass spectrometry has been used as an analytical tool by researchers across various disciplines for decades, its increasing use in clinical laboratories has been a more recent development. The high sensitivity of mass spectrometry has shown value in areas such as drug testing and neonatal screening, and the platform can provide rapid results for providers, and patients.¹

At this year’s Association for Diagnostics and Laboratory Medicine (ADLM) conference Dr. Victoria Zhang, PhD, MBA, DABCC, FADLM outlined exactly what a mass spectrometry workflow involves. She also shared insights into the value and advantages mass spectrometry brings to her patients now, and her thoughts on its future role in the lab. 

The first thing Dr. Zhang is clear to point out is that when we say mass spectrometry it’s not just one thing. She clarifies, “It’s actually a group of various instruments, but they all commonly have three parts.” One unique feature of mass spectrometry is that it can only analyze compounds that are ionized, so that is the first component required. 

An ionization method, such as electrospray ionization, is used to convert molecules to ions. Ions are then sorted and separated according to mass-to-charge (m/z) ratios by a mass analyzer. “Triple quad is one thing that we hear a lot, and the time-of-flight is another analyzer. The goal is the same, to analyze the mass-to-charge ratio,” explains Dr. Zhang. The separated ions are then measured by a detector. The resulting mass spectrum measurement is the m/z ratio of the ions present in a sample, plotted against their intensities and therefore illustrating their relative abundance in the sample.²

Before this stage, however, there are several steps to ensure the process works smoothly. Dr. Zhang likes to begin with the end goal in mind, which is ‘for mass spec to be happy’ and to work efficiently and to its full capacity. The first step in the workflow is sample preparation. “I always see the sample preparation as the most challenging part. If your sample preparation is done well, the rest becomes easy,” she says. 

The next step is chromatography which separates the compounds from each other. “Let's just think about the body fluids,” explains Dr. Zhang, “We have a lot of different substances in human blood. For mass spec to be most effective, we have to separate them. Chromatography can help with that.”

Dr. Zhang frequently finds herself having to explain this process. “I get phone calls from the clinicians saying, ‘Hey, I have this compound in serum, can you measure that for me?’” to which she replies, “It’s not that straightforward!”

In contrast to the mass spectrometry workflow which Dr. Zhang acknowledges as being ‘multi-stepped and labor intensive’, another method used in the clinical laboratory is immunoassays which tend to be more easily automated and require less training.³

She describes immunoassays as ‘very easy to use’. “You can have random access and very high throughput. You put the samples there, you walk away. There's a lot of support also from the vendors, so I think that provides a lot of confidence and ease of use for the customers,” says Dr. Zhang.

However, there are limitations that exist with this method, and she finds there can be a ‘gap between the patient’s needs, versus what the immunoassay can provide’. Dr. Zhang explains that with antibody-based immunoassays, ‘there's some interference that's involved with the assay.’ This susceptibility to interference can lead to the misinterpretation of results.⁴

It is also less specific than mass spectrometry. Dr. Zhang highlights testing for drug abuse as an example. With immunoassays, the results will show only the class of the compounds e.g. opiates. “It’s the class, so in a way, it’s very efficient, but on the other hand you missed the opportunity to identify the individual compounds,” she says, whereas, “You can measure very low levels of compounds much better with mass spectrometry.”

Dr. Zhang believes the choice between the two methods is not straightforward. “It’s like the Swiss Army Knives. You want to have different kinds of tools in your toolbox. I think that's the same way I think about mass spec and immunoassays, you know, as they are really complementary to each other,” she says.

At her core lab which includes an academic medical center with seven affiliated hospitals, Dr. Zhang has found that mass spectrometry provides a ‘great value to the system’. Immunosuppressant drug testing is one example, “That's one of the common drugs that people use, and we have same day turnaround time on mass spec,” she says, which is valuable as the team is processing “hundreds of tests every day.”

Beyond this, the lab also processes Vitamin D testing, and drugs of abuse testing, and has large panel screening for some endocrinology testing as well. “All of them provided great value for our patients,” says Dr. Zhang.

She notes that there are also “a lot more possible applications of mass spectrometry than what we see now.” She highlights endocrinology and testosterone testing in women as an example: “Should that be on mass spec? Should that be on an immunoassay? Well, you can do that on immunoassay, but it's just not as accurate.” Recent clinical papers and guidelines suggest that immunoassays of sex-steroids are inadequate for several patient groups and disease areas, and mass spectrometry steroid assays should be used as a solution.^5,6,7 “Those papers and guidelines really give people the opportunity to understand the value of mass spec,” says Dr. Zhang. 

For providers to feel comfortable making these choices between testing methods, Dr. Zhang believes they need to be educated. “We constantly do this,” she says, explaining that she speaks to new endocrinology residents every year: “They invite me to specifically talk to their residents about mass spectrometry so that they can order the right test. But that’s not true everywhere.”

Dr. Zhang is cautious about where mass spectrometry fits into the lab in the future: “I started the Mass Spectrometry and Separating Science Division when at the time people said ‘Our goal is for mass spectrometry to take over the world’. I'm like ‘That's a great idea, but I don't think that's good for patients.’”

Instead, she believes we need to ‘use the right tool for the right purposes’, and to do this we must start with the patient in mind. “What does the patient need, what kind of assay, and what platform can fulfill the patient's needs? I think that's the fundamental question we have to ask,” she says.

However, she believes if new technology-enabled mass spectrometry becomes more streamlined and more automated, thereby making it more accessible, this approach could change.

She explains that the current workflow for drugs of abuse testing in her lab uses immunoassays for screening, and then mass spectrometry is used as confirmation for any positives found. “If mass spec is as easily accessible as immunoassay and as cost-effective as immunoassay, why do we need the first step? Wouldn't that be nice? So we could take that [first step] out, save some time for the patients, save some money for the patients. You could go directly to the right testing.” This scenario, Dr. Zhang believes, could be ‘a game changer’ for mass spectrometry and the future of laboratory testing. 
 

For a more detailed discussion of the advantages of mass spectrometry and its place in the clinical lab, watch Dr. Zhang’s full presentation.