Supramolecular solvents for making comprehensive liquid-liquid microextraction in multiclass screening methods for drugs of abuse in urine based on liquid chromatography-high resolution mass spectrometry

Soledad González-Rubio; Noelia Caballero-Casero; Ana Ballesteros-Gómez; Darío Cuervo; Gloria Muñoz; Soledad Rubio

doi:10.1016/j.chroma.2023.464061

Supramolecular solvents for making comprehensive liquid-liquid microextraction in multiclass screening methods for drugs of abuse in urine based on liquid chromatography-high resolution mass spectrometry

J Chromatogr A. 2023 Jul 19:1701:464061. doi: 10.1016/j.chroma.2023.464061. Epub 2023 May 9.

Authors

Soledad González-Rubio¹, Noelia Caballero-Casero², Ana Ballesteros-Gómez¹, Darío Cuervo³, Gloria Muñoz³, Soledad Rubio¹

Affiliations

¹ Department of Analytical Chemistry, Instituto Químico para la Energía y el Medioambiente, Marie Curie Building (Annex), Campus of Rabanales, Universidad de Córdoba, Córdoba 14071, Spain.
² Department of Analytical Chemistry, Instituto Químico para la Energía y el Medioambiente, Marie Curie Building (Annex), Campus of Rabanales, Universidad de Córdoba, Córdoba 14071, Spain. Electronic address: a42caasn@uco.es.
³ Doping Control Laboratory. Institute of Health Carlos III, C/ Pintor el Greco S/N, Madrid 28040, Spain.

PMID: 37187096
DOI: 10.1016/j.chroma.2023.464061

Abstract

Multiclass screening methods involving hundreds of structurally unrelated compounds are becoming essential in many control labs and research areas. Accurate mass screening of a theoretically unlimited number of chemicals can be undertaken using liquid chromatography coupled to high resolution mass spectrometry (LCHRMS), but the lack of comprehensive sample treatments hinders this unlimited potential. In this research, the capability of supramolecular solvents (SUPRAS) for making comprehensive liquid-liquid microextraction (LLME) in multiclass screening methods based on LCHRMS was firstly explored. For this purpose, a SUPRAS made up of 1,2-hexanediol, sodium sulphate and water was synthesized directly in the urine and applied to compound extraction and interference removal in the screening of eighty prohibited substances in sports by LC-electrospray ionization-time of flight mass spectrometry. Selected substances included a wide range of polarities (log P from -2.4 to 9.2) and functionalities (e.g. alcohol, amine, amide, carboxyl, ether, ester, ketone, sulfonyl, etc.). No interfering peaks were observed for any of the 80 substances investigated. Around 84-93% of drugs were efficiently extracted (recoveries 70-120%) and 83-94% of the analytes did not show matrix effects (±20%) in the ten tested urines. Method detection limits for the drugs were in the interval 0.002-12.9 ng mL^-1, which are in accordance with the Minimum Required Performance Levels values established by the World Anti-Doping Agency. The applicability of the method was evaluated by the screening of thirty-six blinded and anonymized urine samples, previously analyzed by gas or liquid chromatography-triple quadrupole. Seven of the samples lead to an adverse analytical finding in line with the results obtained by the conventional methods. This research proves that LLME based on SUPRAS constitutes an efficient, economic, and simple sample treatment in multiclass screening methods, an application that is unaffordable for conventional organic solvents.

Keywords: Doping control; LC-ESI-TOF; Screening methods; Supramolecular solvents; Urine.

MeSH terms

Chromatography, Liquid
Liquid Phase Microextraction*
Solvents / chemistry
Spectrometry, Mass, Electrospray Ionization
Urinalysis

Substances

Solvents