Copper nanoparticles for SERS-based determination of some cephalosporin antibiotics in spiked human urine

Copper nanoparticles (CuNPs) were prepared through a wet chemistry method to be used as substituents for noble-metal-based materials in the determination of cephalosporin antibiotics in urine using surface-enhanced Raman spectroscopy (SERS). The synthesis of the CuNPs was optimized to maximize the analytical signal, and microwave heating was used to increase the reaction rate and improve the homogeneity of the CuNPs. Ceftriaxone (CTR), cefazolin (CZL), and cefoperazone (CPR) were used as the analytes of interest. The determination tests were performed on artificially spiked samples of real human urine with concentrations corresponding to therapeutic drug monitoring (TDM) (50–500 μg mL−1). Urine samples collected in the morning and during the day were used to account for deviations in the urine composition, and the universality of the proposed protocol was ensured by performing sample dilution as a pretreatment. The use of calibration plots in the form of Freundlich adsorption isotherms yielded linear calibration plots. All limits of detection were lower than the minimal concentrations required for TDM, equaling 7.5 (CTR), 8.8 (CZL), and 36 (CPR) μg mL−1. Comparison of CuNPs with Ag and Au nanoparticles (AgNPs and AuNPs, respectively) confirmed that CuNPs offered a competitively high Raman enhancement efficiency (for excitation at 638 nm). Further, although the CuNPs demonstrated poorer temporal stability as compared with the AgNPs and AuNPs, the use of freshly prepared CuNPs resulted in satisfactory accuracy (recovery = 93–107%). Given the short analysis time (<20 min, including the time for the synthesis of the CuNPs and the SERS measurements using a portable Raman spectrometer), low sensitivity to the presence of the primary intrinsic urine components and satisfactory figures of merit of the proposed protocol for the determination of cephalosporin antibiotics in urine, it should be suitable for use in TDM.