Ratiometric detection of doxycycline in pharmaceutical based on dual ligands-enhanced copper nanoclusters

A water-soluble, stable, simple and dual ligands (bovine serum albumin and L-histidine)-enhanced copper nanoclusters (BSA-CuNCs@L-His) was synthesized by one-step wet chemical method. Interestingly, the introduction of L-His ligand could improve evidently the quantum yields (QYs, 3.47%) and stability of BSA-CuNCs due to forming the stronger interaction of L-His and Cu and producing bigger diameter CuNCs by coordination-induced aggregation. Thus, a new ratiometric fluorescent probe (RF-probe) was successfully exploited for sensitively and selectively mensurating doxycycline (DOX) because DOX could simultaneously regulate the fluorescence (FL) intensities of BSA-CuNCs@L-His at 410 and 520 nm. The FL quenching of BSA-CuNCs@L-His at 410 nm by DOX was mainly originated from the static quenching process, while DOX could bind to Trp-212 in BSA from the skeleton of BSA-CuNCs@L-His by electrostatic interaction causing the appearance of new emission peak at 520 nm. The content of DOX was monitored by the RF-probe with a linear range of 0.05-14.0 μM and a LOD (limit of detection) and LOQ (limit of quantification) of 6.4 and 21.3 nM (at 3σ/slope and 10σ/slope). Moreover, compared to the standard HPLC method, the proposed RF-probe was extended to the detection of DOX in doxycycline hydrochloride (DOXH) tablets, DOXH injections and DOXH capsules with satisfactory results.