Peptides trapping cocaine: docking simulation and experimental screening by solid phase extraction followed by liquid chromatography mass spectrometry in plasma samples

Two different hexapeptides were computationally designed and tested as selective SPE sorbent for cocaine. The amino acid residues used for designing the two hexapeptides, tested in SPE experiments, were, according to chemical function and interatomic distances, the most (QHWWDW) and the lowest (ESSIDH) preserved sequences in 4 proteins binding cocaine. The hexapeptide–cocaine complex was docked with different scoring functions combinations and resulting binding scores were compared with the SPE results. The extraction procedure for SPE was optimized considering volume loading, pH effect, and human plasma matrix interferences. Cocaine was loaded onto the modified resin cartridge at 10 ng mL−1 and the peptide QHWWDW was found to have the highest recovery with the best retention at pH 7.5, in agreement with docking simulation. Retention experiments were carried out also on cocaine metabolites nor-cocaine, benzoylecgonine and ecgonine methyl ester. Except for nor-cocaine the retention of metabolites on resin modified with peptide QHWWDW decreased drastically confirming the peptide selectivity, and validating the simulation data. Compared to standard solutions, only a slight decrease in cocaine recovery was observed loading human plasma samples after a partial protein precipitation.

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► Two peptides were computationally designed as selective SPE sorbent for cocaine.
► The hexapeptide–cocaine complex was docked with different scoring functions.
► The extraction procedure for SPE was optimized for human plasma.
► QHWWDW was found to have good recovery in agreement with docking simulation.