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Pipette-tip solid-phase extraction coupled with matrix-assisted laser desorption/ionization mass spectrometry enables rapid and high-throughput analysis of antidepressants in rat serum

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Abstract

Therapeutic drug monitoring is essential for ensuring the efficacy and safety of medications. This study introduces a streamlined approach that combines pipette-tip solid-phase extraction (PT-SPE) with matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), facilitating rapid and high-throughput monitoring of drug concentrations. As a demonstration, this method was applied to the extraction and quantification of antidepressants in serum. Utilizing Zip-Tip C18, the method enabled the extraction of antidepressants from complex biological matrices in less than 2 min, with the subsequent MALDI-MS analysis yielding results in just 1 min. Optimal extraction recoveries were achieved using a sampling solution at pH 9.0 and a 10 μL ethanol desorption solution containing 0.1% phosphoric acid. For MALDI analysis, 2,5-dihydroxybenzoic acid was identified as the most effective matrix for producing the highest signal intensity. The quantification strategy exhibited robust linearities (R2 ≥ 0.997) and satisfactory limits of quantification, ranging from 0.05 to 0.5 μg/mL for a suite of antidepressants. The application for monitoring dynamic concentration changes of antidepressants in rat serum emphasized the method’s efficacy. This strategy offers the advantages of high throughput, minimal sample usage, environmental sustainability, and simplicity, providing ideas and a reference basis for the subsequent development of methods for therapeutic drug monitoring.

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Funding

This work was supported by grants from the National Key R&D Program of China (2021YFC2401105), the National Natural Science Foundation of China (No. 82374018, No. 82003921), the China Postdoctoral Science Foundation (2021M702937, 2023M733256), and the Henan Provincial Science and Technology Research Project (242102311184).

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Author notes

  1. Zhi Sun and Fangfang Wang contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China

    Zhi Sun, Fangfang Wang, Ruobing Ren, Peipei Zhou, Qingquan Jia & Lihua Zuo

  2. Henan Key Laboratory of Nanomedicine for Targeting Diagnosis and Treatment, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China

    Wenxuan Li & Di Chen

  3. Shenzhen Bao’an District Center for Disease Control and Prevention, Shenzhen, 518101, China

    Lingguo Zhao

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  1. Zhi Sun
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Contributions

Zhi Sun: writing—original draft. Fangfang Wang: writing—original draft, methodology. Wenxuan Li: methodology. Ruobing Ren: methodology. Peipei Zhou: methodology. Qingquan Jia: methodology. Lingguo Zhao: methodology. Di Chen: conceptualization, writing—review and editing. Lihua Zuo: writing—review and editing.

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Correspondence to Di Chen or Lihua Zuo.

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The collection and utilization of blood samples were carried out in strict adherence to ethical guidelines for the care and use of laboratory animals. The study was approved by the Ethics Committee of Zhengzhou University and executed in collaboration with the First Affiliated Hospital of Zhengzhou University.

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Sun, Z., Wang, F., Li, W. et al. Pipette-tip solid-phase extraction coupled with matrix-assisted laser desorption/ionization mass spectrometry enables rapid and high-throughput analysis of antidepressants in rat serum. Anal Bioanal Chem (2024). https://doi.org/10.1007/s00216-024-05439-x

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