Scientific progress is more than just pushing the boundaries of what’s technically feasible. Innovation is also about advancing what can be done routinely, efficiently, and by a less specialized cohort of users. The latter is the innovation happening right now with mass spectrometry as it becomes a more accessible tool for everyday clinical laboratories.
For decades, mass spectrometry has served as one of the most powerful analytical tools in chemistry, biology, environmental science, and more. It can provide high specificity (less cross-reactivity) and better multi-analyte detection than standard immunochemistry and clinical chemistry assays.1
However, while it delivers high performance, it does not have a reputation for being easy to use.
Workflows are typically manual and highly complex, necessitating specialized mass spec operators. And unlike other mainstream technologies, traditional mass spectrometry systems cannot readily integrate with laboratory information systems (LIS).
Today, with modern automation and greater ease of use, we are finally witnessing the introduction of mass spectrometry into routine clinical lab settings, with standardized platforms that can streamline processes, reduce variability, and simplify operations.
The result: more laboratories can maximize its value, adopting advanced assays, expanding test menus, and delivering faster, more consistent results. For patients and healthcare providers, all of this helps unlock greater access to timely precision medicine.
Moderate complexity
One milestone of this march to routine clinical mass spectrometry use is the recent U.S. FDA categorization of the Ionify steroid assays as “moderate complexity.” A total 25-Hydroxyvitamin D assay recently earned the same moderate categorization late last year.
Clinical laboratory test systems are assigned a moderate or high complexity category on the basis of seven criteria outlined in CLIA regulations.2
During the market authorization or categorization process, the FDA applies these scoring criteria to all commercially available tests, including those that are FDA-cleared, approved, or exempt.
| Moderate complexity refers to a category of diagnostic tests that require a defined level of technical training, procedural rigor, and quality oversight beyond simple waived tests. However, moderate complexity tests do not rise to the sophistication of high-complexity methodologies. The assays are easier to use, typically involving automated instrumentation and some degree of result interpretation (as opposed to just receiving raw spectra or data). |
The new Ionify steroid assay includes analysis of estradiol, DHEA, DHEA-S, progesterone, 17-hydroxyprogesterone, and androstenedione. The assay is run on the cobas i 601 analyzer, a mass spec instrument that serves as a fully automated solution from sample preparation to result reporting. After preparing the system, lab operators simply load the samples into the analyzer.
The system automatically conducts sample preparation, separation, and detection, validating the results and finally transferring to the laboratory information system. As a fully automated and standardized analytical workflow, this mass spectrometry solution achieves the necessary operational simplicity to qualify for CLIA moderate complexity categorization.
By embedding automation into sample prep, analysis, and result handling, the system reduces variability and minimizes operator intervention. Together, these features can lower the technical barrier to entry, enabling more patients can gain access to gold-standard mass spec technology without the need for specialized staff or centralized facilities.
References:
- 1. M J Bennett, J Luong, D W Kinniburgh. B-325 Retrospective Study Comparing Immunoassay Screen and Mass Spectrometry Confirmation Results in an Opioid Dependant Population. Clinical Chemistry, Volume 69, Issue Supplement_1, October 2023, hvad097.644.
- 2. Centers for Disease Control and Prevention. Test complexities. Updated September 11, 2024. Accessed April 1, 2026. https://www.cdc.gov/clia/php/test-complexities/index.html
