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. 2024 Jan 9;29(2):335.
doi: 10.3390/molecules29020335.

Developing and Evaluating the Greenness of a Reliable, All-in-One Thin-Film Microextraction Protocol for Determining Fentanyl, Methadone, and Zolpidem in Plasma, Urine, and Oral Fluid

Krzysztof Goryński  1 , Łukasz Sobczak  2 , Dominika Kołodziej  2
Affiliations

Developing and Evaluating the Greenness of a Reliable, All-in-One Thin-Film Microextraction Protocol for Determining Fentanyl, Methadone, and Zolpidem in Plasma, Urine, and Oral Fluid

Krzysztof Goryński et al. Molecules. .

Abstract

This paper proposes an all-in-one microextraction-based protocol capable of determining and quantifying fentanyl, methadone, and zolpidem in plasma, urine, and saliva at concentrations below those required by international regulatory organizations. A homemade thin-film microextraction device featuring an octyl-cyanopropyl stationary phase was coupled with LC-MS/MS. The proposed method was developed and validated according to FDA criteria, providing extraction efficiency values ranging from 26.7% to 76.2% with no significant matrix effects (2.6% to 15.5% signal suppression). The developed protocol provided low limits of quantification (mostly equal to 1 ng mL-1) and good reproducibility (intra- and inter-day RSDs of less than 9.6% and 12.0%, respectively) and accuracy (89% to 104% of the test concentration). An assessment of the protocol's environmental impact indicated that attention must be devoted to eliminating the use of toxic reagents and developing its capability for in situ sampling and in-field analysis using portable instruments. The proposed TFME-based protocol provides clinical laboratories with a versatile, one-step tool that enables the simultaneous monitoring of fentanyl, methadone, and zolpidem using the most popular biological matrices.

Keywords: LC-MS/MS; blood; fentanyl; methadone; opioids; oral fluid; overdosing; solid-phase microextraction; urine; zolpidem.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Figure 1
Figure 1
Comparison of different types of coatings (n = 3, extract from PBS, desorption solvent can/water/FA 80:19.9:0.1 v/v/v; desorption and extraction times were 150 and 120 min, respectively, in all cases).
Figure 2
Figure 2
Schematic presentation of the all-in-one thin-film microextraction protocol coupled with LC-MS technique. Parameters used with TFME protocol summarized in Figure 3.
Figure 3
Figure 3
Parameters used in final protocol.
Figure 4
Figure 4
Chromatograms at lower quantification limits. Zolpidem: 1 μg L−1 in oral fluid; 3 μg L−1 in plasma and urine. Fentanyl: 3 μg L−1 in oral fluid; 1 μg L−1 in plasma and urine. Methadone: 3 μg L−1 in oral fluid; 1 μg L−1 in plasma; and 3 μg L−1 in urine.
Figure 5
Figure 5
Green assessment of the TFME-LC-MS/MS protocol applying (a) the GAPI tool, (b) the ComplexGAPI tool, (c) the BAGI tool, (d) the AGREE metric, and (e) the AGREEprep metric.
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