Coupling of micro-solid-phase extraction and internal extractive electrospray ionization mass spectrometry for ultra-sensitive detection of 1-hydroxypyrene and papaverine in human urine samples

  • Jing Han
  • Wei Liu
  • Rui Su
  • Lixue Zhu
  • Debo WuEmail author
  • Jiaquan Xu
  • Aiying Liu
  • Hua Zhang
  • Wei Kou
  • Xiaoping Zhang
  • Shuiping Yang
Research Paper


Quantification of ultra-trace analytes in complex biological samples using micro-solid-phase extraction followed by direct detection with internal extractive electrospray ionization mass spectrometry (μSPE–iEESI–MS) was demonstrated. 1-Hydroxypyrene (1-OHP) and papaverine at attomole levels in human raw urine samples were analyzed under negative and positive ion detection mode, respectively. The μSPE was simply prepared by packing a disposable syringe filter with octadecyl carbon chain (C18)-bonded micro silica particles, which were then treated as the “bulk sample” after the analytes were efficiently enriched by the C18 particles. Under the optimized experimental conditions, the analytes were readily eluted by isopropanol/water (80/20, V/V) at a high voltage of ± 4.0 kV, producing analyte ions under ambient conditions. The limit of detection (LOD) was 0.02 pg/L (9.2 amol) for 1-hydroxypyrene and 0.02 pg/L (5.9 amol) for papaverine. The acceptable linearity (R2 > 0.99), signal stability (RSD ≤ 10.7%), spike recoveries (91–95%), and comparable results for real urine samples were also achieved, opening up possibilities for quantitative analysis of trace compounds (at attomole levels) in complex bio-samples.

Graphical abstract


μSPE Urine Enrichment Ultra-sensitive iEESI–MS/MS Detection limit 



This work was supported by the National Natural Science Foundation of China (No. 21605016, 21705017), International Science & Technology Cooperation Program of China (No. 2015DFA40290), and Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT) (No. IRT_17R20).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

All procedures performed in this work involving human participants were in accordance with the ethical standards of the research committee of East China University of Technology and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants from the local Bureau of Drug Abuse Control (BDAC) included in the study.

Supplementary material

216_2019_1794_MOESM1_ESM.pdf (456 kb)
ESM 1 (PDF 455 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Jing Han
    • 1
    • 2
  • Wei Liu
    • 2
  • Rui Su
    • 1
  • Lixue Zhu
    • 1
  • Debo Wu
    • 2
    Email author
  • Jiaquan Xu
    • 2
  • Aiying Liu
    • 1
  • Hua Zhang
    • 1
  • Wei Kou
    • 1
  • Xiaoping Zhang
    • 2
  • Shuiping Yang
    • 2
  1. 1.State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of ChemistryJilin UniversityChangchunChina
  2. 2.Jiangxi Key Laboratory for Mass Spectrometry and InstrumentationEast China University of TechnologyNanchangChina

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