TY - JOUR
T1 - Report from the HarmoSter study
T2 - Impact of calibration on comparability of LC-MS/MS measurement of circulating cortisol, 17OH-progesterone and aldosterone
AU - Fanelli, Flaminia
AU - Cantù, Marco
AU - Temchenko, Anastasia
AU - Mezzullo, Marco
AU - Lindner, Johanna M.
AU - Peitzsch, Mirko
AU - Hawley, James M.
AU - Bruce, Stephen
AU - Binz, Pierre-Alain
AU - Ackermans, Mariette T.
AU - Heijboer, Annemieke C.
AU - van den Ouweland, Jody
AU - Koeppl, Daniel
AU - Nardi, Elena
AU - Mackenzie, Finlay
AU - Rauh, Manfred
AU - Eisenhofer, Graeme
AU - Keevil, Brian G.
AU - Vogeser, Michael
AU - Pagotto, Uberto
N1 - Funding Information: Research funding: This study was supported by the Regione Emilia-Romagna (doi.org/10.13039/501100009879), Alessandro Liberati Young Researcher Grants (grant number: PRUA 1-2012-004, granted to FF) and by Deutsche Forschungsgemeinschaft (DFG; doi.org/10.13039/501100001659), German Research Foundation (grant number: 314061271-CRC/TRR 205/1, granted to MP and GE). Publisher Copyright: © 2022 Flaminia Fanelli et al., published by De Gruyter, Berlin/Boston.
PY - 2022/4/1
Y1 - 2022/4/1
N2 - Objectives: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is recommended for measuring circulating steroids. However, assays display technical heterogeneity. So far, reproducibility of corticosteroid LC-MS/MS measurements has received scant attention. The aim of the study was to compare LC-MS/MS measurements of cortisol, 17OH-progesterone and aldosterone from nine European centers and assess performance according to external quality assessment (EQA) materials and calibration. Methods: Seventy-eight patient samples, EQA materials and two commercial calibration sets were measured twice by laboratory-specific procedures. Results were obtained by in-house (CAL1) and external calibrations (CAL2 and CAL3). We evaluated intra and inter-laboratory imprecision, correlation and agreement in patient samples, and trueness, bias and commutability in EQA materials. Results: Using CAL1, intra-laboratory CVs ranged between 2.8-7.4%, 4.4-18.0% and 5.2-22.2%, for cortisol, 17OH-progesterone and aldosterone, respectively. Trueness and bias in EQA materials were mostly acceptable, however, inappropriate commutability and target value assignment were highlighted in some cases. CAL2 showed suboptimal accuracy. Median inter-laboratory CVs for cortisol, 17OH-progesterone and aldosterone were 4.9, 11.8 and 13.8% with CAL1 and 3.6, 10.3 and 8.6% with CAL3 (all p<0.001), respectively. Using CAL1, median bias vs. all laboratory-medians ranged from -6.6 to 6.9%, -17.2 to 7.8% and -12.0 to 16.8% for cortisol, 17OH-progesterone and aldosterone, respectively. Regression lines significantly deviated from the best fit for most laboratories. Using CAL3 improved cortisol and 17OH-progesterone between-method bias and correlation. Conclusions: Intra-laboratory imprecision and performance with EQA materials were variable. Inter-laboratory performance was mostly within specifications. Although residual variability persists, adopting common traceable calibrators and RMP-determined EQA materials is beneficial for standardization of LC-MS/MS steroid measurements.
AB - Objectives: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is recommended for measuring circulating steroids. However, assays display technical heterogeneity. So far, reproducibility of corticosteroid LC-MS/MS measurements has received scant attention. The aim of the study was to compare LC-MS/MS measurements of cortisol, 17OH-progesterone and aldosterone from nine European centers and assess performance according to external quality assessment (EQA) materials and calibration. Methods: Seventy-eight patient samples, EQA materials and two commercial calibration sets were measured twice by laboratory-specific procedures. Results were obtained by in-house (CAL1) and external calibrations (CAL2 and CAL3). We evaluated intra and inter-laboratory imprecision, correlation and agreement in patient samples, and trueness, bias and commutability in EQA materials. Results: Using CAL1, intra-laboratory CVs ranged between 2.8-7.4%, 4.4-18.0% and 5.2-22.2%, for cortisol, 17OH-progesterone and aldosterone, respectively. Trueness and bias in EQA materials were mostly acceptable, however, inappropriate commutability and target value assignment were highlighted in some cases. CAL2 showed suboptimal accuracy. Median inter-laboratory CVs for cortisol, 17OH-progesterone and aldosterone were 4.9, 11.8 and 13.8% with CAL1 and 3.6, 10.3 and 8.6% with CAL3 (all p<0.001), respectively. Using CAL1, median bias vs. all laboratory-medians ranged from -6.6 to 6.9%, -17.2 to 7.8% and -12.0 to 16.8% for cortisol, 17OH-progesterone and aldosterone, respectively. Regression lines significantly deviated from the best fit for most laboratories. Using CAL3 improved cortisol and 17OH-progesterone between-method bias and correlation. Conclusions: Intra-laboratory imprecision and performance with EQA materials were variable. Inter-laboratory performance was mostly within specifications. Although residual variability persists, adopting common traceable calibrators and RMP-determined EQA materials is beneficial for standardization of LC-MS/MS steroid measurements.
KW - 17OH-progesterone
KW - aldosterone
KW - calibration
KW - cortisol
KW - external quality control
KW - harmonization
KW - inter-laboratory performance
KW - liquid chromatography-tandem mass spectrometry
KW - method comparison
KW - steroid hormones
UR - http://www.scopus.com/inward/record.url?scp=85126019734&partnerID=8YFLogxK
UR - https://pure.uva.nl/ws/files/120580537/suppl_j_cclm_2021_1028_suppl.zip
U2 - https://doi.org/10.1515/cclm-2021-1028
DO - https://doi.org/10.1515/cclm-2021-1028
M3 - Article
C2 - 35172417
SN - 1434-6621
VL - 60
SP - 726
EP - 739
JO - Clinical chemistry and laboratory medicine
JF - Clinical chemistry and laboratory medicine
IS - 5
ER -