Ultrasensitive turn-off fluorescent sensor for estimation of the new influenza antiviral prodrug baloxavir marboxil in its pharmaceutical formulation

Abstract

Carbon quantum dots (CQDs) are a recently developed class of fluorescent nanoparticles made from carbon. Co-doping with heteroatoms such as nitrogen and sulfur improved the properties and generated a high quantum yield. In the proposed study, we utilized a simple, cost-effective, single-stage hydrothermal approach to produce extreme photoluminescence co-doped, nitrogen and sulfur, CQDs (N,S-CODs). Thiosemicarbazide was used as a nitrogen and sulfur source, while citric acid was used as a carbon source to produce fluorescent probes. The prepared N,S-CQDs were subjected to extensive characterization. The generated N,S-CQDs yielded strong fluorescence emission at λ _em 430.0 nm after excitation at λ _ex 360.0 nm, with a relatively high quantum yield of 41.3% utilizing quinine sulfate as a reference fluorescent compound. These N,S-CQDs were applied as fluorescent nanosensors for the ultrasensitive spectrofluorimetric determination of baloxavir marboxil (BXM) directly without pre-derivatization for the first time. BXM effectively quenches the native fluorescence of N,S-CQDs. Considering the optimal conditions, the fluorescence intensity reduction of N,S-CQDs exhibited a 'turn-off' response to BXM at concentrations of 10.0-100.0 ng ml^-1, with detection limits of 1.88 ng ml^-1 and quantitation limits of 5.69 ng ml^-1, respectively. The proposed method determined BXM successfully in its tablet dosage form and further expanded to confirm the content uniformity of the tablet units in agreement with USP guidelines.

Keywords: baloxavir marboxil; content uniformity; fluorescent; nanosensors; nitrogen–sulfur–carbon quantum dots.

Figure 1.

Chemical structure of baloxavir marboxil (BXM).

Figure 2.

High-resolution transmission electron microscopy images of the prepared N,S-CQDS at different magnifications. Scale bars: (a) 50 nm, (b) 100 nm, and (c) 200 nm.

Figure 3.

(a) UV–visible absorption spectra of N,S-CQDS (i), TSC (ii) and CA (iii). (b) Fluorescence emission spectrum of N,S-CQDs at 430.0 nm after excitation at 360.0 nm. (c) Fluorescence spectra of N,S-CQDs at different excitation wavelengths.

Figure 4.

(a) Energy-dispersive X-ray spectrum of synthesized N,S-CQDs and (b) Fourier transform infrared spectrum presenting the surface functionality of N,S-CQDs.

Figure 5.

Fluorescence emission spectra of N,S-CQDs in aqueous solution upon addition of various concentrations of BXM (from top to bottom: 0, 10.0, 20.0, 30.0, 40.0, 50.0, 60.0 and 100.0 ng ml⁻¹).

Figure 6.

Greenness, blueness and whiteness assessment of (a) the proposed spectrofluorimetric and (b) the reported high-performance liquid chromatography (HPLC) [36] methods via AGREE, BAGI and RGB 12 whiteness tools. R, red; G, green; B, blue; LOD, limit of detection; LOQ, limit of quantification.