Addressing Emerging Diagnostic Trends with Clinical LC-MS-MS

The coronavirus pandemic ushered in a new wave of patient sampling and testing trends. While remote sampling and personalized patient monitoring using micro-sampling techniques like dried blood spots and sample matrices, such as breath, saliva, urine, and hair, have created opportunities for novel collection devices, these innovations have also led to new technical hurdles for clinical diagnostic testing.

Advances in tandem mass spectrometry combined with liquid chromatography (LC-MS-MS) offer unique analytical advantages to address these emerging diagnostic trends. Covering a wide range of analytes in clinical toxicology, endocrinology, inborn errors of metabolism (IEM), and therapeutic drug monitoring (TDM), LC-MS-MS can provide the analytical sensitivity and selectivity needed to tackle the sample volume, type, and throughput needs of clinical labs.

Small molecule detection via LC-MS-MS

For small molecule detection, LC-MS-MS can provide substantial benefits, including 

1. improved analytical sensitivity at low concentrations (e.g., female testosterone), 
2. improved analytical specificity between similar compounds (e.g., steroid hormones and drugs of abuse), and
3. increased ability to multiplex (e.g., drugs of abuse confirmation panels, steroid hormones, TDM).

Large molecule detection via LC-MS-MS

For large molecule detection, LC-MS-MS offers the ability to 

1. detect and differentiate between different protein isoforms (e.g., growth hormone), 
2. overcome “auto-antibody” effects (e.g., thyroglobulin), and 
3. multiplex several analytes in one test (e.g., oncology biomarkers for specificity and targeted therapeutics).

Meeting clinical lab requirements

Despite these advantages, clinical LC-MS-MS platforms still require additional advancements to meet widespread clinical lab adoption requirements. This continued development includes modular automation, such as sample preparation modules, for lab compatibility and integration, and sample handling, for improved flexibility/prioritization and increased turnaround time. 

For instance, current analysis of large molecules often involves a relatively complex and lengthy sample preparation process. Before these tests become widely adopted, they will have to be simplified and automated for ease of use by clinical lab technicians.

Current test menus will also need to be broadened for economic viability (price per test) of the investment. In addition, widespread support from the clinical diagnostics industry through connectivity and informatics, workflow automation, and education will be required to drive greater clinical LC-MS-MS adoption.

Becoming a leading diagnostics tool

Nonetheless, increased use of LC-MS-MS technology for biomarker discovery in proteomics, metabolomics, and lipidomics research suggests that clinical MS has the potential to emerge as a leading diagnostics tool in high-value, high-impact disease states, such as oncology and neurology. LC-MS-MS is uniquely positioned to differentiate protein isoforms and post-translational modifications and measure protein quantities—areas not easily detected or assessed by other clinical detection technologies.

Over the next decade, as LC-MS-MS providers begin to overcome lingering hurdles associated with automation and sample prep simplification, we suspect that the benefits of clinical MS—analytical sensitivity, selectivity, and multiplexing—will be fully realized and more widely adopted. By combining current LC-MS-MS benefits with streamlined workflows, shortened turnaround times, and a broad cost-effective menu of total solutions, LC-MS-MS will soon become a prominent technology in tomorrow’s clinical labs.