Mixed-mode cationic exchange paper combined with direct infusion mass spectrometry, a sustainable approach to determine opioids in biosamples

Abstract

Direct infusion mass spectrometry (DI-MS/MS) allows the rapid analysis of samples and minimizes solvent usage by avoiding chromatographic separation. However, it is prone to ion suppression due to matrix effects, especially when biosamples are processed. In this context, sample preparation appears as the perfect complement to get proper analytical results. In this article, a novel and sustainable planar sorptive phase containing mixed-mode cationic exchange (MCX) particles is presented to overcome the limitations of DI-MS/MS in bioanalysis. The new phase uses cellulose paper as a natural substrate over which the particles can be retained using polyacrylonitrile (PAN) as the chemical binder. The high porosity of the cellulose substrate simplifies the synthesis since a straightforward dip-coating technique can be applied. For this purpose, MCX particles are initially dispersed in a PAN solution prepared in N,N-Dimethylformamide. A segment of paper is later introduced into the slurry, and the evaporation of the solvent leaves a film of PAN-MCX composite over the paper, where the particles are entrapped but accessible for the analyte's isolation. The resulting MCX-paper has been evaluated for the extraction of selected opioids (codeine, methadone, morphine, naloxone, oxycodone, and tramadol) from saliva and urine samples and their determination by direct infusion tandem mass spectrometry. Working at the optimized conditions, the limits of detection were in the low μg L−1 range. The precision, expressed as relative standard deviation, was better than 12 % under intra-day and inter-day conditions. The accuracy, expressed as relative recoveries, provides values in the ranges 89–113 % and 74–121% for saliva and urine, respectively. The method was finally applied to analyze saliva and urine samples collected from patients under codeine treatment.