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A simple method for rapid screening and diagnosis of common organic acidemias: quantitative detection of serum and urine organic acid profiles based on liquid chromatography-tandem mass spectrometry

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Abstract

Organic acid (OA) analysis is a specific test for inherited metabolic disorders (IMDs); however, the previous detection methods are laborious and costly. This study aims to develop a rapid method for the simultaneous quantification of serum and urine OA profiles. The method was established based on the liquid chromatography-tandem mass spectrometry (LC–MS/MS) technique. The specificity, sensitivity, robustness, and accuracy of the established method were validated. Fifteen healthy subjects and nine IMD patients were measured for clinical validation. OAs with their intrinsic isomers were completely separated. The LC–MS/MS analysis time was 5.5 min. Calibration curves were linear within the ranges of 27.00 μg/g for all OAs. The average correlation relationship (R) varied from 0.9891 to 0.9998. The limit of detection and limit of quantification varied from 0.003 to 0.07 μg/g and 0.006 to 0.08 μg/g, respectively. No obvious carryover was observed. The intra-assay, inter-assay, and total imprecisions were 1.22–4.14%, 0.90–5.20%, and 1.67–5.90%, respectively. The mean spiked recovery at the three levels varied from 94.31 to 106.68%. The matrix effects can be compensated for by internal standard correction. Nine IMD patients were identified. A robust LC–MS/MS method for the rapid determination of serum and urine OA profiles without derivatization or liquid–liquid extraction was developed and validated. The analysis of five common OAs can be completed in short minutes. This innovative LC–MS/MS method for OA profiles may present its potential in future rapid screening and diagnosis of IMDs.

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Acknowledgements

We are grateful for the kind help from Dr. Xueyan Han (Department of Medical Statistics, Peking University First Hospital, Beijing, China) in language editing.

Funding

This work was supported by the National Key Research and Development Program of China (2018YFC1002204).

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Authors and Affiliations

  1. National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, 100730, People’s Republic of China

    Lizi Jin, Zhenni Liu, Jie Zeng, Haijian Zhao, Jiangtao Zhang, Tianjiao Zhang & Chuanbao Zhang

  2. Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Dahua Road, Beijing, 100730, People’s Republic of China

    Lizi Jin, Zhenni Liu, Jie Zeng, Haijian Zhao, Jiangtao Zhang, Tianjiao Zhang & Chuanbao Zhang

  3. Inner Mongolian Maternity and Child Health Care Hospital, Inner Mongolia, People’s Republic of China

    Bo Zhu

  4. Zhejiang Biosan Biochemical Technologies Co., Ltd, Zhejiang, People’s Republic of China

    Yu Zhang

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  1. Lizi Jin
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  2. Zhenni Liu
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  3. Jie Zeng
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  4. Haijian Zhao
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  7. Yu Zhang
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  8. Tianjiao Zhang
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  9. Chuanbao Zhang
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All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

Corresponding authors

Correspondence to Tianjiao Zhang or Chuanbao Zhang.

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Ethics approval

The study was approved by the Ethics Committee of Beijing Hospital.

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The authors declare no competing interests.

Source of biological material

Validation samples were collected in the Department of Laboratory Medicine of Beijing Hospital; patient samples were donated by Inner Mongolian Maternity and Child Health Care Hospital; Zhejiang Biosan Biochemical Technologies Co., Ltd.

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Jin, L., Liu, Z., Zeng, J. et al. A simple method for rapid screening and diagnosis of common organic acidemias: quantitative detection of serum and urine organic acid profiles based on liquid chromatography-tandem mass spectrometry. Anal Bioanal Chem 414, 7823–7837 (2022). https://doi.org/10.1007/s00216-022-04316-9

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  • DOI: https://doi.org/10.1007/s00216-022-04316-9

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