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. 2022 Jan 15:1189:123088.
doi: 10.1016/j.jchromb.2021.123088. Epub 2021 Dec 22.

Analysis of sodium 2-mercaptoethane sulfonate in rat plasma using high performance liquid chromatography tandem-mass spectrometry

Abigail B Donkor  1 , Carl W White  2 , Heidi J Nick  2 , Brian A Logue  3
Affiliations

Analysis of sodium 2-mercaptoethane sulfonate in rat plasma using high performance liquid chromatography tandem-mass spectrometry

Abigail B Donkor et al. J Chromatogr B Analyt Technol Biomed Life Sci. .

Abstract

Sodium 2-mercaptoethane sulfonate (MESNA) is a thiol-containing compound that has proven to be effective in inactivating acrolein, the toxic metabolite of some anti-cancer drugs (e.g., cyclophosphamide and ifosphamide). Also, it scavenges free radicals which cause numerous disorders by attacking biological molecules. Current methods available to analyze MESNA in biological matrices include colorimetry and high-performance liquid chromatography (HPLC) with ultraviolet, fluorescence, or electrochemical detection. These methods have several limitations including low sensitivity, poor selectivity, a high degree of difficulty, and long analysis times. Hence, a rapid, simple, and sensitive HPLC tandem mass spectrometry (MS/MS) method was developed and validated to quantify MESNA in rat plasma following IP administration. The analysis of MESNA was accomplished via plasma protein precipitation, centrifugation, supernatant evaporation, reconstitution, and HPLC-MS/MS analysis. The method showcases an outstanding limit of detection (20 nM), excellent linearity (R2 = 0.999, and percent residual accuracy >90%) and a wide linear range (0.05-200 μM). The method also produced good accuracy and precision (100 ± 10% and <10% relative standard deviation, respectively). The validated method was successfully used to analyze MESNA from treated animals and will allow easier development of MESNA for therapeutic purposes.

Keywords: Antineoplastic; Chemoprotectant; Free radical; LC-MS/MS; Method development.

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Conflict of interest statement

Declaration of interests

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.
ESI (−) product ion mass spectra of MESNA (a) and 3-MPS (b) with identification of the abundant ions. Molecular ions of MESNA and 3-MPS [M–H]− correspond to 140.40 and 154.70 m/z, respectively. The ([M–2H]−) of MESNA and 3-MPS also correspond to 138.9 m/z and 153 m/z, respectively. Insets, structures of MESNA (a) and 3-MPS (b) with abundant fragments indicated.
Figure 1.
Figure 1.
ESI (−) product ion mass spectra of MESNA (a) and 3-MPS (b) with identification of the abundant ions. Molecular ions of MESNA and 3-MPS [M–H]− correspond to 140.40 and 154.70 m/z, respectively. The ([M–2H]−) of MESNA and 3-MPS also correspond to 138.9 m/z and 153 m/z, respectively. Insets, structures of MESNA (a) and 3-MPS (b) with abundant fragments indicated.
Figure 2.
Figure 2.
Representative HPLC-MS/MS chromatograms of spiked (5 μM) and non-spiked (a) MESNA and (b) 3-MPS (IS) in rat plasma. The chromatograms show signal response to the MRM transitions of MESNA (140.40 → 79.9 and 140.40 → 138.9 m/z) and 3-MPS (154.70 → 80.0 and 154.70 → 93.9 m/z).
Figure 2.
Figure 2.
Representative HPLC-MS/MS chromatograms of spiked (5 μM) and non-spiked (a) MESNA and (b) 3-MPS (IS) in rat plasma. The chromatograms show signal response to the MRM transitions of MESNA (140.40 → 79.9 and 140.40 → 138.9 m/z) and 3-MPS (154.70 → 80.0 and 154.70 → 93.9 m/z).
Figure 3.
Figure 3.
HPLC-MS/MS chromatogram from the plasma of MESNA-treated rats and rat plasma obtained prior to MESNA treatment. The chromatograms represent signal response to MRM quantification transition of (a) MESNA (140.40 → 79.9 m/z) and (b) 3-MPS (154.70 → 80.0).
Figure 3.
Figure 3.
HPLC-MS/MS chromatogram from the plasma of MESNA-treated rats and rat plasma obtained prior to MESNA treatment. The chromatograms represent signal response to MRM quantification transition of (a) MESNA (140.40 → 79.9 m/z) and (b) 3-MPS (154.70 → 80.0).
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