Innovative Mixed-Mode Cationic Exchange Sorptive Tapes Enable Accurate Detection of Opioids in Saliva Samples

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Mixed-mode cationic exchange (MCX) sorptive tapes combined with direct infusion mass spectrometry enable selective extraction and rapid analysis of cationic compounds in complex samples, such as opioids in saliva.

Researchers from the Universidad de Córdoba in Spain have made a significant breakthrough in the field of bioanalysis with the development of mixed-mode cationic exchange (MCX) sorptive tapes combined with direct infusion mass spectrometry. Led by Rafael Lucena and Soledad Cárdenas, this pioneering study focuses on accurately determining opioids, specifically methadone and tramadol, in saliva samples. The findings published in the Journal of Chromatography A have far-reaching implications for forensic and clinical applications (1).

MCX sorptive tapes consist of a solid support material functionalized with both cation exchange and hydrophobic moieties. These tapes allow for the selective extraction of cationic analytes from complex samples, such as biological fluids or environmental matrices. The extracted analytes are then directly infused into a mass spectrometer for identification and quantification, enabling rapid and sensitive analysis without the need for extensive sample preparation. This approach offers a versatile and efficient method for targeted analysis of cationic compounds in various fields, including pharmaceuticals, environmental monitoring, and clinical research.

The team of scientists successfully synthesized MCX tapes as sorptive phases for bioanalysis. These tapes were created by utilizing aluminum foil as a substrate, which was then covered with double-sided adhesive tape where the MCX particles (approximately 1.4 ± 0.2 mg) were firmly attached. The MCX particles possess unique properties that facilitate the extraction of analytes at physiological pH, taking advantage of the positive charges of both drugs while minimizing the potential co-extraction of endogenous matrix compounds.

To optimize the extraction process, the researchers thoroughly investigated key variables such as ionic strength, extraction time, and sample dilution. The outcomes were remarkable, with the method achieving exceptional sensitivity. The team attained detection limits as low as 3.3 μg·L−1 using direct infusion mass spectrometry as the instrumental technique. Moreover, the precision of the method, expressed as relative standard deviation, exceeded expectations, surpassing a value of 3.8%. The accuracy of the analysis, expressed as relative recoveries, exhibited a range from 83% to 113%.


Excitingly, the developed method was successfully applied to determine tramadol levels in saliva samples collected from patients undergoing medical treatment. The utilization of MCX sorptive tapes combined with direct infusion mass spectrometry demonstrated its potential in accurately quantifying opioids in a complex matrix.

The significance of this research lies in the opportunity it presents for the convenient preparation of sorptive tapes using commercially available or custom-synthesized sorbent particles. This novel approach showcases the potential for further advancements in analytical techniques, offering improved detection and monitoring of opioids in various forensic and clinical scenarios.


(1) Calero-Cañuelo, C.; Casado-Carmona, F. A.; Lucena, R.; Cárdenas, S. Mixed-mode cationic exchange sorptive tapes combined with direct infusion mass spectrometry for determining opioids in saliva samples. J. Chromatogr. A 2023, 1702, 464097. DOI: