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Translation

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Contact:
Dr. Julia Dittrich 
E-Mail: Julia.Dittrich@medizin.uni-leipzig.de
Phone​: +49 341 - 97 22461

1) Scope and success criteria

​A core goal of our working group is the translational implementation of LC-MS/MS methods from research into fully accredited routine diagnostics. Successful translation requires not only analytical sensitivity and selectivity, but also robustness, standardization, high-throughput capability, and seamless integration into clinical workflows.​

2) Established routine example: therapeutic drug monitoring

One longstanding example is the high-throughput quantification of the immunosuppressive drugs cyclosporine A, tacrolimus, everolimus and sirolimus in whole blood. Our LC-MS/MS method applied for therapeutic drug monitoring is in continuous routine clinical operation for more than 20 years. Designed for robustness and scalability, the assay reliably operates under real-world routine conditions while fulfilling external quality assessment requirements.​

3) Translational milestone: steroid hormone profiling

Steroid hormone analysis represents another important translational milestone. The successful transfer of steroid profiling from research-based applications into accredited routine diagnostics demonstrated that analytical complexity can be reduced without compromising diagnostic performance, enabling the replacement of selected immunoassays by LC–MS/MS.​

4) Strategic outlook: MS-based protein quantification in routine laboratory medicine

Looking forward, our translational focus extends beyond small-molecule quantification. A strategic objective of our group is the implementation of MS-based protein quantification into routine laboratory medicine. In contrast to uniparametric immunoassays, targeted proteomics enables multiplexed panel measurements, allowing comprehensive characterization of metabolic pathways—particularly when protein panels are interpreted jointly with metabolite profiles.​

5) Example and standardization pathway: apolipoproteins and metrological traceability

A prominent example is the multiplexed quantification of apolipoproteins using quantotypic peptides. We developed and validated a high-throughput LC-MS/MS assay that simultaneously quantifies 12 apolipoproteins in human plasma. The method has been applied in large-scale epidemiological studies comprising several thousand samples, demonstrating robustness and scalability. However, routine implementation of MS-based protein quantification requires metrological traceability and harmonized calibration hierarchies. Our group therefore contributes as a reference laboratory to the IFCC working group on apolipoproteins by mass spectrometry, aiming at the standardization of clinically relevant apolipoproteins by the establishment of a SI-traceable reference measurement system.​


Translational Implementation of Steroid Hormone LC-MS/MS into Routine Diagnostics:

The transition of steroid hormone analysis from research-focused LC-MS/MS applications to fully accredited routine diagnostics requires more than analytical sensitivity and selectivity. It demands robustness, standardization, high-throughput capability, and integration into existing clinical laboratory workflows.

Building on a rapid online SPE-LC-MS/MS(/MS) platform with a total run time below 5 minutes and minimal sample preparation, we established a multi-matrix steroid profiling method applicable to serum, saliva, and urine. The combination of simple protein precipitation, automated column switching, and selective MS²/MS³ detection enabled precise quantification across clinically relevant concentration ranges while maintaining routine-compatible throughput.

Crucially, the method was developed under routine conditions: commercially available calibrators and quality control materials were implemented, analytical performance was benchmarked against immunoassays, and validation was aligned with national quality assurance guidelines.

Systematic differences between immunoassays and LC-MS/MS – particularly in low concentration ranges and in the presence of structurally related medication – highlighted the superior analytical specificity of mass spectrometry and its direct clinical relevance.

The translational step consisted in reducing analytical complexity without compromising diagnostic performance: minimizing sample volume, avoiding derivatization, shortening chromatographic run time, and ensuring compatibility with external quality assessment schemes. This approach enabled the replacement of selected immunoassays by LC-MS/MS in routine endocrine diagnostics and facilitated the establishment of reliable reference intervals.

By combining analytical innovation with clinical validation and quality harmonization, steroid hormone mass spectrometry was successfully transferred from a specialized research tool into a robust, high-throughput diagnostic platform.

Reference Method Steroids:

LeCMS has been involved in the development of LC-MS/MS reference measurement procedures for steroid hormones in collaboration with Roche Diagnostics. Within this collaboration, eleven reference methods were established, validated, and successfully published in Clinical Chemistry and Laboratory Medicine, contributing to the standardization and harmonization of steroid hormone measurements.

Liebigstr. 27a, Sockelgeschoss
04103 Leipzig
Phone:
+49 341 97 22254
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