MSACL 2025 Abstract

Analytical Accuracy Evaluation of Six Routine Lipid Assays Based on CRMLN-Certified ID-GC/MS and Abell-Kendall Reference Methods

Yeo-Min Yun (1), Jong Do Seo (1), Sang-Guk Lee (2), Chan-Ik Cho (3), Hyung-Doo Park (4), Kyunghoon Lee (5), Junghan Song (5)
(1) Department of Laboratory Medicine, Konkuk University School of Medicine, Konkuk University Medical Center, Seoul, Korea; (2) Department of Laboratory Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea; (3) National Medical Reference Laboratory, Division of Chronic Disease Prevention, Korea Disease control and prevention Agency; (4) Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; (5) Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seoul National University School of Medicine, Seongnam, Korea

Yeo-Min Yun, MD, PhD (Presenter) Konkuk University School of Medicine

Relevant Financial Disclosures (within past 24 months, reported on Jul 17, 2025) No relevant financial relationship(s) to disclose. Conflict mitigation NOT REQUIRED.

BACKGROUND:
Lipid testing, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) is a cornerstone of cardiovascular risk assessment and chronic disease management. However, the clinical utility of lipid tests relies heavily on their accuracy and comparability across laboratories. Standardization using reference measurement procedures (RMPs) is essential, and isotope dilution gas chromatography–mass spectrometry (ID-GC/MS) is widely recognized as the gold standard for lipid quantification due to its superior specificity, precision, and traceability.

METHODS:
Six routine lipid assays (Roche, Beckman, Siemens, Sekisui, Wako, Kyowa) were evaluated for TC, TG, HDL-C, and LDL-C using three types of serum matrices: fresh single-donor, frozen single, and pooled serum. Reference values for TC and TG were determined by the Korean National Medical Reference Laboratory (NMRL), a CRMLN- and JCTLM-accredited laboratory, using the ID-GC/MS method in accordance with CDC and international protocols. This method provides high-order traceability and has been internationally validated for its long-term stability and analytical robustness. HDL-C and LDL-C reference values were determined using the CDC-modified Abell–Kendall and ultracentrifugation-based reference methods. The mean percentage bias (%bias) of each assay was calculated.

RESULTS:
For total cholesterol, five of six MPs exhibited acceptable mean %bias within the NCEP criterion of ±3%. Wako showed the largest negative bias (–3.87%), while Sekisui had the highest positive bias (+1.71%). Triglyceride measurements also met the NCEP allowable limit of ±5%, with mean %bias ranging from –3.68% (Wako) to +1.29% (Kyowa). These results indicate high analytical accuracy and standardization for TC and TG assays across all platforms.

In contrast, HDL-C and LDL-C results showed greater variability. HDL-C assays from Siemens (+7.41%) and Wako (–5.87%) exceeded the NCEP accuracy limit of ±5%, suggesting limitations in standardization for HDL-C. For LDL-C, Beckman showed the highest positive bias (+5.89%), while Kyowa displayed the largest negative bias (–4.14%). These deviations exceeded the NCEP recommended bias limit of ±4%, particularly in frozen pooled serum specimens with elevated TG levels. The findings underscore the impact of matrix effects and sample-dependent performance variability, especially for lipoprotein-based measurements.

DISCUSSION & CONCLUSION:
The use of ID-GC/MS in reference measurement plays a pivotal role in the standardization of lipid assays. Unlike routine enzymatic methods, ID-GC/MS offers unmatched analytical specificity and is unaffected by matrix interferences, enzymatic variability, or reagent lot differences. As a primary reference method, it enables direct linkage of patient results to certified reference materials, ensuring long-term traceability and international comparability.

This study demonstrates that routine assays for TC and TG, when anchored to ID-GC/MS-derived reference values, can achieve high accuracy and meet international quality targets. The stability and reproducibility of ID-GC/MS data also support its application in external quality assessment (EQA) programs and development of commutable reference materials. In contrast, the persistent variability in HDL-C and LDL-C assays highlights the need for further refinement of reference procedures and broader adoption of traceable calibration systems.

In conclusion, expanding the use of ID-GC/MS in reference measurement is essential to advance lipid assay standardization. Its continued application by CRMLN-certified laboratories will enhance diagnostic accuracy, support public health monitoring, and ultimately contribute to better clinical outcomes through more reliable lipid testing.