Humic acid-coated paper: An affordable mixed-mode weak-cation exchanger for isolating cocaine, codeine, and methadone from saliva samples for their direct infusion mass spectrometric analysis.

The use of natural materials as precursors for synthesizing sorptive phases can reduce the environmental impact of the sample preparation step. In this article, two natural materials, i.e., cellulose and humic acids, are combined, resulting in a porous and flat sorptive phase that combines hydrophobic and cation exchange interactions. The simple preparation, with low reagent consumption, and the high production capacity make this process affordable. The performance of the humic acid-coated paper has been studied towards three basic drugs (cocaine, codeine, and methadone), and it has allowed the determination of the targets in saliva by direct infusion tandem mass spectrometry. The simultaneous extraction of many samples and the rapid analysis (2 min) provide a high sample throughput. The resulting method has been validated following the International Conference on Harmonization (ICH) M10 validation guide. Working at the optimum conditions, the linear range was established from 5 to 500 μg·L and the detection limits were established at 1.5 μg·L for all the analytes. At the LOQ, the inter-day precision and intra-day precision, expressed as relative standard deviation, were better than 13.6% and 17.9%, respectively. For low/mid/high quality controls, the inter-day precision and intra-day precision were better than 11.8% and 9.1%, respectively. The accuracy, calculated as relative recovery, was in the range of 83.8-106.1%. Several samples from patients under treatment with codeine-containing prescriptions were finally analyzed.