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Development of human serum matrix-based unconjugated estriol-certified reference material by recommended ID-LC-MS/MS reference method

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Abstract

To solve long-term lack of traceability of commercial calibrator kits and standardize clinical routine assays, we developed a human serum matrix-based unconjugated estriol (uE3) reference material (RM) with five concentration gradients. The RMs of uE3 were certified by the National Institute of Metrology (NIM) with the codes of GBW (E) 091048, GBW (E) 091049, GBW (E) 091050, GBW (E) 091051, and GBW (E) 091052. The RMs were determined by isotope dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) reference method which was developed in our group and recommended by the Joint Committee on Traceability on Laboratory Medicine (JCTLM). GBW09224 is intended for use as a primary reference material to enable the SI-traceable measurement of uE3. This study describes the development process of these certified RMs. The candidate material was prepared by collecting from the remaining serum samples after routine clinical testing. Satisfactory homogeneity and stability were shown in these RMs. They are also commutable between the reference method and the three routine clinical immunoassay systems. To improve the accuracy of value assignment, a collaborative study in nine reference laboratories was conducted which was performed according to ISO/WD 15725-1 and all of the reference laboratories have been confirmed by China National Accreditation Service for Conformity Assessment (CNAS). The raw results were statistically analyzed and processed, coupled with uncertainty evaluation, to obtain the certified value: GBW (E) 091048 is 22.1 ± 1.3 nmol/L, GBW (E) 091049 is 33.6 ± 1.6 nmol/L, GBW (E) 091050 is 10.4 ± 0.8 nmol/L, GBW (E) 091051 is 15.5 ± 1.0 nmol/L, GBW (E) 091052 is 47.0 ± 2.0 nmol/L.

Graphical abstract

The preparation process of human serum matrix-based reference material and the lack of these type of secondary (commutable) reference material of unconjugated estriol lead to the interruption of its traceability chain, which is a problem to be solved in its standardization as mentioned in the metrological traceability in ISO 17511, 2020.

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Abbreviations

RM:

Reference material

CRM:

Certified reference material

GUM:

Guide to the Expression of Uncertainty in Measurement

JCTLM:

Joint Committee on Traceability on Laboratory Medicine

IFCC:

International Federation of Clinical Chemistry and Laboratory Medicine

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Acknowledgements

We greatly appreciate the following reference laboratories which participated in the collaborative study of value assignment of the RM: Beijing Institute of Medical Device Testing Opto-Mechatronics Industrial (ISO/IEC 17025 accreditation CNAS: L6477); Beijing Aerospace General Hospital (ISO/IEC 17025 accreditation CNAS:L5536); Beijing Strong Biotechnologies, Inc. (ISO/IEC 17025 accreditation CNAS:L11846); Shanghai Center For Clinical Laboratory (ISO/IEC 17025 accreditation CNAS: L6730); Center of Laboratory Medicine Affiliated Hospital of Nantong University (ISO/IEC17025 accreditation CNAS: L6260); Maccura Biotechnology (ISO/IEC 17025 accreditation CNAS: L6172); MedicalSystem Biotechnology Co., Ltd.; Reference Laboratory (ISO/IEC 17025 accreditation CNAS: L8377); Autobio Diagnostics Co. Ltd Zhengzhou Eco&Tech Zone (ISO/IEC 17025 accreditation CNAS:L13885).

Funding

This research was supported by The National Key Research and Development Program of China (2021YFC2009300, 2021YFC2009305), the National Natural Science Foundation of China (81572088), the Natural Science Foundation of Guangdong Province (2020A1515010667), the Specific Research Fund for TCM Science and Technology of Guangdong Provincial Hospital of Chinese Medicine (YN2019QL01 and YN2019 MJ04), and the Administration of Traditional Chinese Medicine Bureau of Guangdong Province (20211150).

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Authors and Affiliations

  1. Department of Laboratory Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, 510120, China

    Qiaoxuan Zhang, Haibiao Lin, Jun Yan, Min Zhan, Fen Ouyang, Peifeng Ke, Liqiao Han, Junhua Zhuang & Xianzhang Huang

  2. State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China

    Qiaoxuan Zhang & Haibiao Lin

  3. Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, 510120, China

    Kai Bai & Meiran Wu

Authors
  1. Qiaoxuan Zhang
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  2. Kai Bai
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  3. Meiran Wu
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  4. Haibiao Lin
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  5. Jun Yan
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  6. Min Zhan
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  7. Fen Ouyang
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  9. Liqiao Han
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  10. Junhua Zhuang
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  11. Xianzhang Huang
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Corresponding authors

Correspondence to Liqiao Han, Junhua Zhuang or Xianzhang Huang.

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Ethics approval

The research involved plasma samples taken from pregnant women, and this study is approved by the Ethics Committee of the Second Affiliated Hospital of Guangzhou University of Chinese Medicine. The number of this review is ZE2019-149-01.

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The ethics committee approved the exemption of informed consent.

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The authors declare no competing interests.

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Zhang, Q., Bai, K., Wu, M. et al. Development of human serum matrix-based unconjugated estriol-certified reference material by recommended ID-LC-MS/MS reference method. Anal Bioanal Chem 414, 2523–2531 (2022). https://doi.org/10.1007/s00216-022-03896-w

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