MSACL 2017 EU Abstract

Application of LC-MS/MS in Routine Clinical Diagnostics: Has it Lived Up the Expectations?

Eef Lentjes (Presenter)
University Medical Center Utrecht

Bio: Eef Lentjes studied Chemistry and Medicin at the University of Nijmegen, the Netherlands. Following graduation, he started training in clinical chemistry at the Leiden University Medical Center (LUMC). He was registered as a clinical chemist in 1989 and he was registered as clinical chemist endocrinologist in 2005. In 1999 he finished his PhD project at the Leiden Univerity, entitled “Cortisol. Bioavailability and receptors in stress-related disorders” From 1989 to 2002 he worked in the endocrine laboratory in the Laboratory of Clinical Chemistry at the LUMC and from 2001 he was acting head of the department. In 2002 he moved to the Laboratory of Clinical Chemistry & Hematology at the University Medical Center Utrecht. There, he is responsible for the endocrine laboratory and laboratory for special techniques. In 2015 he became chair of the Endocrine Section of the Dutch Foundation for Quality Assessment in Medical Laboratories (SKML)

Authorship: Eef Lentjes1, Jody van den Ouweland2 and Hong Bui3
1University Medical Centrum Utrecht; 2Canisius-Wilhelmina Ziekenhuis Nijmegen, 3Stichting AtalMedial, Hoofddorp Medisch, the Netherlands

Short Abstract

We have investigated the performance of LC-MS/MS in comparison to immunoassays by analysis of 8 year data since the introduction of the LC-MS/MS method, from the Dutch EQAS for Endocrinology. The number of LCMSMS users is increasing each year and about 100 results are produced now per scheme by about 15 LCMSMS users. although accuracy has much improved, between laboratory CV is mostly higher for the LCMSMS group compared to immunoassay methods. We conclude that optimization and better standardization is necessary for LCMSMS methods.

Long Abstract


Liquid chromatography-tandem mass spectrometry (LC-MS/MS) recently has also found its way in the diagnostic laboratories for the measurement of hormones, a field dominated by commercially available immunoassays. LC-MS/MS is a highly sensitive and specific technique for the quantitative analysis of hormones with low cross reactivity compared to immunoassays and is often considered the gold standard measurement technique in hormone analysis.


We have investigated the performance of LC-MS/MS in comparison to immunoassays by analysis of 8 year data since the introduction of the LC-MS/MS method, from the Dutch EQAS for Endocrinology. The section organizes 6 schemes annually with two frozen serum samples for the hormones in each scheme. All laboratory trimmed means, CV’s and mean and CV per method are calculated.


Each year the number of laboratories using an LC-MS/MS participating in the Dutch EQA scheme for hormones increases. In 2017 about 15 laboratories make use of an LC-MS/MS and about 100 results per scheme are determined by this method. For cortisol in urine, 17 hydroxyprogesterone and androstenedion 50 to 60% of the results are now from LC-MS/MS. In The Netherlands, LC-MS/MS is only used for steroids, (nor)metanephrines and vitamin D. The absolute values of steroids in the samples containing low concentrations (e.g. testosterone or 17 hydroxyprogesterone < 1 nmol/L) are mostly lower in LC-MS/MS participants compared to the immunoassay methods, probably due to less cross reactivity. Between-laboratory CV, however is often higher for the LC-MS/MS group compared to the immunoassay methods (e.g. 10% vs 5%). In addition, not all laboratories perform equally well using this technique and now and then outliers are detected in the LC-MS/MS determined results.

Conclusions & Discussion

It can be concluded that the number of laboratories with an LC-MS/MS increases steadily. Although this technique shows much improvement in accuracy, introduction of the LC-MS/MS is not a guarantee for better performance. Considerable challenges with regard to standardization and reproducibility exist. Many methods are in-house developed assays and several components of the measurement procedure, e.g. preparation of calibrators, use of a proper internal standard, samples preparation, and chromatographic separation have to be optimized and standardized. Traceability to a reference measurement procedure or a reference preparation is needed and will probably enhance analytical performance.

References & Acknowledgements:

Financial Disclosure

Board Memberno

IP Royalty: no

Planning to mention or discuss specific products or technology of the company(ies) listed above: