Mass Spectrometry: Transitioning from Bench to Bedside to Improve Patient Care


Mass spectrometry (MS) is rapidly transitioning from specialized testing to being broadly applied in the clinical laboratory. This shift has improved the practice of laboratory medicine and enabled physicians to provide better patient care. In a recent review published in Clinical Chemistry, a Mayo Clinic researcher and a University of California–SanDiego clinical chemist discuss the historical evolution and future applications of mass spectrometry in the clinical laboratory.

Paul Jannetto, Ph.D.
Paul Jannetto, Ph.D.

“Mass spectrometry is really beginning to play a permanent and transformative role in laboratory medicine,” says Mayo biochemist Paul Jannetto, Ph.D., who co-authored the article entitled, “Effective Use of Mass Spectrometry in the Clinical Laboratory.”

“You’re seeing this technology being incorporated into more and more mid-sized hospital labs and even local physician-operated labs instead of just large academic hospitals or reference laboratories. And in the future, I see MS being just like any other automated clinical chemical analyzer for measuring glucose—in that every-sized hospital or laboratory would use one.”

The major impetus that moved mass spectrometry from the research laboratory to the clinical laboratory happened on May 26, 1981, when an EA-6B Prowler jet crashed while landing on the aircraft carrier USS Nimitz. Fourteen servicemen were killed and 45 injured. Subsequent immunoassay tests revealed that a large percentage of urine samples from servicemen were positive for marijuana metabolites. This prompted President Ronald Reagan to develop a zero tolerance for drugs of abuse in the military. Due to a large number of false-positive immunoassay results, antibody-based drug screens began to be considered “presumptive” until confirmed by gas chromatography–mass spectrometry (GC-MS). Several studies also demonstrated that urine drug testing was cost-effective. The requirement for GC-MS confirmation drove the development of MS in toxicology laboratories, where it also began to be used for therapeutic drug monitoring.

“We’ve come a long way from the original GC-MS days, where we were basically just looking at drugs of abuse,” says Dr. Jannetto. “Now, we’re looking at a variety of novel biomarkers for proteomics, autoimmunity, oncology, and genomics. These MS platforms offer us an alternative methodology that we couldn’t do with any other technology.”

According to the review, MS technologies have dramatically improved the time required for microbial identifications. This evolution, driven by continuous improvements in analytical platforms, is anchored by the analytical specificity of MS. Also, with increasing economic pressures and decreasing laboratory test reimbursement, mass spectrometry testing continues to provide cost-effective solutions.

“Laboratories that develop MS tests can avoid the clinical limitations and potentially higher costs associated with immunoassay tests,” says Dr. Jannetto. Hospital laboratories performing higher-volume tests could also potentially decrease send-out costs by bringing those tests in-house.

Further, the ability to develop multi-analyte panels using a single MS method offers additional time, labor, and expense savings.

However, even as MS continues to make significant contributions to patient care, some substantial challenges remain, such as the high capital cost of equipment, requirements for a skilled labor force, lack of automation, and regulatory uncertainty. As these applications move from research laboratories into clinical practice, a host of infrastructure needs to be developed.

Despite the challenges, mass spectrometry has a bright future in laboratory medicine, especially as vendors simplify these MS platforms.

“You won’t have to be an expert because there will eventually be more FDA-approved kits for MS where the method is already fully developed so labs can just validate it—use it right out of the box,” says Dr. Jannetto. “So you’re going to see mass spectrometry instruments becoming more like clinical chemistry analyzers. Once that happens, it will take some of the regulatory restrictions and implementation challenges away. And so, theoretically, smaller and mid-sized labs will be able to do many of the same tests in-house that previously only large reference labs could do.”

Dr. Jannetto offers the example of a patient in a local hospital’s transplant program who has just received a new liver or heart. Instead of that hospital having to send the patient’s blood sample to a larger institution and waiting on immunosuppressive test results, “its laboratory could do the monitoring in-house and get those sample values back much more quickly—information that will help the health care provider in determining treatment options for the patient,” he says.

“It would allow clinicians to make dosage adjustments quicker on transplant patients to minimize rejection and or toxicity. Clinicians could do this in real time at their own local institution, using these FDA-approved platforms and assays. I really foresee this having a huge positive impact on patient care.”

Christoph Bahn

Christoph Bahn

Christoph Bahn covers emerging research and discovery for Mayo Clinic Laboratories. His writing has also appeared in The New York Times, Los Angeles Times, and Smithsonian Air & Space. He divides his time between Southern California and Northwest Ohio.