Novel B,N-doped carbon quantum dot fluorescence quenching method for sensitive and green determination of lisinopril: mechanistic insights from quantum calculations and sustainable analytical approach

Abstract

A novel, sensitive, and environmentally friendly fluorescence quenching method was developed for lisinopril determination using boron and nitrogen co-doped carbon quantum dots (B,N CQDs) as fluorescent probes. The B,N CQDs exhibited uniform nanoparticles with mean diameter of 3.97 nm and intense blue fluorescence with maximum excitation at 360 nm and emission at 429 nm. Upon increasing lisinopril concentration, a quenching of the B,N CQDs fluorescence was observed in a concentration-dependent manner. The fluorescence quenching mechanism was investigated through Stern–Volmer analysis, thermodynamic studies, and quantum mechanical calculations. Static quenching via ground-state complex formation was confirmed with Stern–Volmer constants (K_sv) decreasing from 7.94 × 10⁵ to 5.48 × 10⁵ M⁻¹ as temperature increased from 298 to 313 K. Quantum mechanical studies using the PM6 method revealed binding energy of −33.58 kJ mol⁻¹, in excellent agreement with experimental thermodynamic parameters (ΔG = −35.01 kJ mol⁻¹). Two distinct interaction sites were identified: amino group of lisinopril with carboxylic group of B,N CQDs (4.4 Å) and carboxylic group of lisinopril with boron atom (3.6 Å). Experimental conditions were optimized using Box–Behnken response surface methodology. The developed method demonstrated a linear range of 0.02–2.0 μg mL⁻¹, detection limit of 6.21 ng mL⁻¹, and quantification limit of 18.63 ng mL⁻¹. Method validation according to ICH Q2(R2) guidelines confirmed satisfactory accuracy (98.14 ± 0.857%) and precision (RSD < 1.25%). The method was successfully applied to commercial tablets and spiked plasma samples with excellent recovery (97.46–103.64%). Comprehensive greenness assessment using Analytical GREEnness Metric (AGREE), Modified Green Analytical Procedure Index (MoGAPI), Blue Applicability Grade Index (BAGI), and Click Analytical Chemistry Index (CACI) yielded scores of 0.77, 80%, 77.5, and 70, respectively. This work represents the first report of B,N CQDs for lisinopril determination, offering cost-effectiveness, room-temperature operation, and superior environmental profile.