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High-sensitivity detection of therapeutic drugs in complex biofluids using a packed ballpoint-electrospray ionization technique

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Abstract

A simple and sensitive C18 packed ballpoint-electrospray ionization (PBP-ESI) technique was developed for biofluid analysis. In this technique, the configuration of a commercial ballpoint consisting of a hollow chamber, an intermediate socket, and a metal ball was fully exploited. The rear-end hollow chamber was used for loading C18 adsorbent and sample, and the front metal ball served as a spray emitter for online ionization. The good electrical conductivity of the metal body allowed high voltage to be conveniently applied to the ballpoint without inserting the electrode into the solution for electrical connection. Urine sample was directly analyzed with the C18 packed ballpoint; plasma and whole blood samples were premixed with C18 adsorbent before being packed into the ballpoint for detection. As a result of the sample cleanup by C18 adsorbent, the salt matrix in the urine sample as well as the phospholipid and protein matrices in plasma and whole blood samples was significantly reduced. The lower limits of quantitation (LLOQs) for urine, plasma, and whole blood samples reached the subnanogram-per-milliliter level.

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Funding

Dr. Yan Zhou received funding from the National Natural Science Foundation of China (21572221 and 21772193) and National Key R&D Program of China grant no. 2018YFC1602400. Dr. Bing Xia received funding from the National Natural Science Foundation of China (21672206).

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Authors and Affiliations

  1. Chengdu Institute of Biology, Chinese Academy of Sciences, No. 93 South Keyuan Road, Gaoxin Distinct, Chengdu, 610041, Sichuan, China

    Xian Fu, Bing Xia, Yu Wang, Peiyu Shi & Yan Zhou

  2. University of Chinese Academy of Sciences, Beijing, 100049, China

    Xian Fu, Yu Wang & Peiyu Shi

  3. GCP Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China

    Yongping Qin

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  1. Xian Fu
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  2. Yongping Qin
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  3. Bing Xia
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  4. Yu Wang
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  6. Yan Zhou
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Corresponding authors

Correspondence to Yongping Qin or Yan Zhou.

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Research involving human participants

Human plasma and whole blood were donated by West China Hospital, Sichuan University (Chengdu, China). Informed consent and sampling permission were obtained prior to specimen collection, and the experiments on human biologic samples were approved by the Ethics Committee of Chengdu Institute of Biology, Chinese Academy of Sciences.

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Fu, X., Qin, Y., Xia, B. et al. High-sensitivity detection of therapeutic drugs in complex biofluids using a packed ballpoint-electrospray ionization technique. Anal Bioanal Chem 412, 2711–2720 (2020). https://doi.org/10.1007/s00216-020-02512-z

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  • DOI: https://doi.org/10.1007/s00216-020-02512-z

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