Recent Applications of Quantum Dots in Pharmaceutical Analysis.

Nanotechnology has emerged as one of the most potential areas for pharmaceutical analysis. The need for nanomaterials in pharmaceutical analysis is comprehended in terms of economic challenges, health and safety concerns. Quantum dots (QDs)or colloidal semiconductor nanocrystals are new groups of fluorescent nanoparticles that bind nanotechnology to drug analysis. Because of their special physicochemical characteristics and small size, QDs are thought to be promising candidates for the electrical and luminescent probes development. They were originally developed as luminescent biological labels, but are now discovering new analytical chemistry applications, where their photo-luminescent properties are used in pharmaceutical, clinical analysis, food quality control and environmental monitoring. In this review, we discuss QDs regarding properties and advantages, advances in methods of synthesis and their recent applications in drug analysis in the recent last years.

A novel sustainable second-derivative synchronous spectrofluorimetric method for the simultaneous determination of olmesartan medoxomil and rosuvastatin calcium in bulk and formulations: Integrated greenness and whiteness evaluation.

The present research has established a quick and highly sensitive second-derivative synchronous fluorometric technique for the simultaneous quantification of a binary mixture of olmesartan medoxomil and rosuvastatin calcium. Simultaneously, the suggested approach was used to detect the synchronous fluorescence intensity of the cited drugs at Δ λ = 80 nm in ethanol to determine the concentrations of olmesartan medoxomil and rosuvastatin calcium at 265 and 240 nm, respectively. Various experimental conditions were tested, and each variable was analyzed and optimized. The calibration graphs were shown to be linear within ranges of 0.1-2.0 and 0.5-6.0 µg ml-1 for each drug concentration, respectively. The newly developed Green Solvents Selecting Tool (GSST) was utilized to assess the solvent's sustainability. Furthermore, the proposed method was found to be environmentally friendly after being evaluated with three different tools [the Green Analytical Procedure Index (GAPI), the Analytical Greenness Metric (AGREE), and the Analytical Eco-Scale with Eco-score equal to 95]. The whiteness qualities were also studied using the Red-Green-Blue (RGB12) model, which was recently designed and showed a high score equal to 92.9. The proposed method's good findings, as well as its ongoing sustainability, simplicity, and economy, stimulate its application in QC laboratories.

Probing the potential toxicity of trimetazidine by characterizing its interaction with human serum albumin.

The small molecular drugs pharmacodynamics and pharmacokinetics could be affected by human serum albumin (HSA) transport, so we studied the interaction between HSA and the widely used anti-ischemic agent, trimetazidine (TMZ), using different approaches. As shown by synchronous fluorescence spectroscopy, the interaction affects the microenvironment confirmation around tyrosine residues. The site-competitive experiments showed that TMZ had an affinity toward subdomain III A (site II) of HSA. The enthalpy and entropy changes (ΔH and ΔS), which were 37.75 and 0.197 K J mol-1, respectively, showed that the predominant intermolecular interactions are hydrophobic forces. According to FTIR research, the interaction between HSA and TMZ caused polypeptide carbonyl-hydrogen bonds to rearrange. The HSA esterase enzyme activity was decreased with TMZ. Docking analysis confirmed the site-competitive experiments and thermodynamic results. This study demonstrated that TMZ interacted with HSA, and the structure and function of HSA were influenced by TMZ. This study could aid in understanding the pharmacokinetics of TMZ and provide basic data for safe use.

Multi-spectroscopic, thermodynamic and molecular docking studies to investigate the interaction of eplerenone with human serum albumin.

The binding of small molecular drugs with human serum albumin (HSA) has a crucial influence on their pharmacokinetics. The binding interaction between the antihypertensive eplerenone (EPL) and HSA was investigated using multi-spectroscopic techniques for the first time. These techniques include ultraviolet-visible (UV-vis) spectroscopy, Fourier-transform infrared (FTIR), native fluorescence spectroscopy, synchronous fluorescence spectroscopy and molecular docking approach. The fluorescence spectroscopic study showed that EPL quenched HSA inherent fluorescence. The mechanism for quenching of HSA by EPL has been determined to be static in nature and confirmed by UV absorption and fluorescence spectroscopy. The modified Stern-Volmer equation was used to estimate the binding constant (Kb ) as well as the number of bindings (n). The results indicated that the binding occurs at a single site (Kb = 2.238 × 103 L mol-1 at 298 K). The enthalpy and entropy changes (∆H and ∆S) were 58.061 and 0.258 K J mol-1 , respectively, illustrating that the principal intermolecular interactions stabilizing the EPL-HSA system are hydrophobic forces. Synchronous fluorescence spectroscopy revealed that EPL binding to HSA occurred around the tyrosine (Tyr) residue and this agreed with the molecular docking study. The Förster resonance energy transfer (FRET) analysis confirmed the static quenching mechanism. The esterase enzyme activity of HSA was also evaluated showing its decrease in the presence of EPL. Furthermore, docking analysis and site-specific markers experiment revealed that EPL binds with HSA at subdomain IB (site III).

One-pot synthesis of fluorescent nitrogen and sulfur-carbon quantum dots as a sensitive nanosensor for trimetazidine determination.

Water-soluble and highly stable N,S-doped CQDs (N,S-CQDs) were synthesized using a low-cost strategy with citric acid and thiosemicarbazide in one step for use as a fluorescent nanosensor. The achieved N,S-CQDs produced strong emission at 446 nm upon excitation at 370 nm and a high quantum yield of 58.5%. The quenching effect on the prepared N,S-CQDs was utilized for determination of trimetazidine (TMZ) spectrofluorimetrically over a wide linear range 0.04-0.5 µM (0.0106-0.133 µg ml-1 ) and a low limit of detection of 0.01 µM (0.002 µg ml-1 ). Furthermore, CDs were used as a simple and rapid fluorescent probe to determine TMZ in its pharmaceutical formulations as well as in human plasma. The method was tested in compliance with International Council for Harmonisation guidelines. The results obtained were compared statistically with those given for a reported method showing no significant variation regards accuracy and precision.

A Novel Eplerenone Ecofriendly Fluorescent Nanosensor Based on Nitrogen and Sulfur-Carbon Quantum Dots.

In this work, a novel ecofriendly optical nanosensor for detection of Eplerenone (EPL) in biological samples was reported. Highly luminescent water-soluble nitrogen and sulfur doped carbon quantum dots (N, S-CQDs) have been prepared successfully. The synthesis was based on the reaction of thiosemicarbazide (TS) as source of N and S and citric acid (CA) as source of carbon in one-step aqueous base reflux treatment. The produced N, S-CQDs have a small particle size in the range of 4.7 nm with a high quantum yield (58.5%) and high emission intensity at 446 nm under excitation wavelength of 370 nm. The unique properties of N, S-CQDs make them useful tool as a nano fluorescent probe for sensitive determination of EPL. EPL has been found to decrease the fluorescence of S, N-CDs significantly through static quenching according to the Stern - Volmer plot. The decreased intensity of S, N-CDs fluorescence was proportional to EPL in the 0.2-3.0 µM range. The limit of detection and quantitation were 0.05 and 0.15 µM, respectively. The assay of EPL by this approach was successfully done in drug formulations and in spiked human serum samples.

The use of green spectroscopy with multivariate calibration models for simultaneous analysis of ternary drug mixture in combined oral antidiabetic pill.

In this work, different chemometric calibration models were developed and validated for the purpose of determining of ternary mixture of oral antidiabetic drugs; vildagliptin (VDG), saxagliptin (SAX) and sitagliptin phosphate (STG). The used models were Partial least squares (PLS) and Artificial Neural Networks (ANN). However, on these various models the impact of genetic algorithm (GA) as a form of variable selection was also investigated. The UV spectral data was used as basis in the quantitative study of the drugs analyzed in bulk and product formulations. The concentration range of the calibration curves of VDG, SAX and STG were 10-22 µg mL-1, 24-40 µg mL-1 and 82-130 µg mL-1, respectively. The calibration set included nineteen mixtures and the others six were used as a validation set to test the predictability of the developed multivariate models. The validation parameters of the evaluated methods were statistically determined. For the analysis of drugs studied in laboratory-prepared mixtures and their dosage forms, PLS-1, GA-PLS-1, ANN, and GA-ENN were successfully employed. The results obtained by the developed methods were compared to those given by a reported method and there were no statistically significant differences regarding accuracy and precision.