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Brinzolamide (BRZ) is an antiglaucoma drug also used by athletes for doping purposes; therefore, it is prohibited by the World Anti-Doping Agency. Consequently, the presence of BRZ or its metabolites in athletes' urine constitutes a violation of anti-doping rules. The current work presents a novel electrochemical method that assesses the effectiveness of mercury oxide nanoparticles (HgO-NPs) and a mercuric chloride-1,10-phenanthroline complex (HgCl 2 -Phen complex) as sensors for BRZ analysis. A comparative analysis revealed that the synthesized HgCl 2 -Phen complex exhibited superior sensitivity and efficiency in determining BRZ levels. The properties of the modifiers were extensively characterized using elemental analysis, X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, and scanning electron microscopy (SEM). Furthermore, electrochemical characterization was conducted using square wave voltammetry (SWV), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). The electrode showed a good response for SWV evaluations of BRZ in a concentration range of 0.1 to 6.0 μmol L -1 , with very low limits of detection (0.01 μmol L -1 ) and quantitation (0.031 μmol L -1 ). The method's applicability was validated by detecting BRZ in urine samples from healthy human volunteers and in pharmaceutical eye drops. Additionally, the practical effectiveness of the method was assessed using the blue applicability grade index (BAGI). The key advantages of this sensor include its simple manufacturing process, as well as its remarkable sensitivity and selectivity., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

This study introduces a remarkably simple, green, and highly sensitive inclusion complex based spectrofluorimetric method for analyzing two sodium glucose cotransporter-2 (SGLT2) inhibitors: empagliflozin (EGF) and dapagliflozin (DGF). The method utilizes beta-cyclodextrin (β-CD) complexation to enhance the native fluorescence of EGF and DGF in aqueous solutions, resulting in 11.0-fold and 9.0-fold intensity increases, respectively. Fluorescence measurements were conducted at 301 nm emission following 230 nm excitation for both drugs. The method demonstrates excellent linearity (0.9994 for EGF and 0.9993 for DGF) over concentration ranges of 5.0-250.0 ng/mL and 10.0-300.0 ng/mL, with low detection limits of 1.05 and 1.38 ng/mL for EGF and DGF, respectively. The method's versatility was validated through successful application in pharmaceutical formulations, content uniformity testing, and biological fluids. This eco-friendly approach primarily uses water as a solvent and requires minimal reagents. The method's environmental impact was comprehensively evaluated using the analytical eco-scale, green analytical procedure index (GAPI), and analytical greenness metric (AGREE)., (© 2024 John Wiley & Sons Ltd.)

The new drug linagliptin belongs to the class of dipeptidyl peptidase-4 enzyme inhibitors. Linagliptin is used to treat type 2 diabetes and is taken orally either alone or in combination with other drugs. In this instance, a new, simple, and economical technique for analyzing linagliptin was developed by the effective use of a pyrrolidone derivative. The primary amine group of linagliptin permits its condensation with ninhydrin (0.14% w/v) to produce a fluorescent product in the presence of phenylacetaldehyde (0.02% v/v). All experimental parameters were carefully examined and adjusted in order to monitor the generation of the pyrrolidone derivative at excitation and emission wavelengths of 385 and 475 nm, respectively. The calibration graph was made by plotting the intensity of the fluorescence in relation to linagliptin concentration. A significant linearity was found for values ranging from 20 to 460 ng/mL. The process's validity has been verified by a thorough assessment of the instructions provided by the International Conference on Harmonization (ICH). The results indicate excellent uniformity with a reference method, showing that there is no substantial difference in precision and accuracy. The proposed approach was utilized for determining linagliptin in real rat plasma successfully owing to its high sensitivity. Additionally, the proposed approach was evaluated using the Eco-Scale evaluation tool and showed a high degree of eco-friendliness (86/100)., (© 2023 John Wiley & Sons Ltd.)

The present study was designed to evaluate the potential protective effects of the cysteinyl leukotriene receptor blocker montelukast (MNK) and the xanthine oxidase inhibitor febuxostat (FBX) and their combination on a model of acute gouty arthritis induced by intraarticular injection of monourate sodium crystal (MUC) injection in rats. Additionally, we established an HPTLC method for the quantitative determination of both drugs simultaneously and applied this method to detect this combination in rat plasma. In this study, the treated male Wistar rats were grouped as follows: a negative control group injected with phosphate buffer saline (PBS) and a positive control group injected with MUC in their tibiotarsal joint. Four groups were treated orally with diclofenac (4 mg kg-1), MNK (10 mg kg-1), FBX (5 mg kg-1) and MNK plus FBX before MUC injection in their tibiotarsal joints. MUC injection in joints without pretreatment led to a progressive significant increase in joint diameter and heavy leucocytic infiltration compared to the PBS-injected joints. Treatment with diclofenac or a combination of MNK and FBX significantly decreased both joint diameters and leucocytic infiltration compared to the MUC group. MNK or FBX treatment attenuated leucocytic infiltration and significantly decreased joint diameters compared to the MUC group. Thus, MNK and FBX can prevent the development of MUC-induced acute gouty arthritis in rats. Also, MNK can be an alternative preventive treatment, particularly in elderly patients who cannot tolerate NSAIDs or corticosteroid. Furthermore, a new thin-layer chromatographic method combined with fluorescence detection was developed and validated for the simultaneous estimation of a mixture of FBX and MNK in spiked human plasma. In this method, we employed TLC aluminium plates precoated with silica gel G 60F254 as the stationary phase and chloroform : methanol (9 : 1, v/v) as the mobile phase. The optimized mobile phase selected for development gives compact bands (Rf values are 0.28 and 0.63 for FBX and MNK, respectively). The emission intensities were measured using a K400 optical filter after excitation at 322 nm. The linear regression data for the calibration plots showed excellent linear relationship (r = 0.9990 and 0.9996 for FBX and MNK, respectively), and the linearity range was 10.0-800.0 ng per band for both drugs. According to ICH-guidelines, this method was validated for precision, accuracy, robustness and selectivity. Also, the limits of detection and quantitation were calculated. In addition, stability studies on the studied mixture were performed. Statistical analysis proved that this method is reproducible and selective for the estimation of a mixture of FBX and MNK.

Sofosbuvir (SOF) and daclatasvir (DCS) are novel, recently developed direct acting antiviral agents characterized by potent anti-hepatitis C virus action. A fast and efficient HPLC-UV method was developed, validated and applied for simultaneous determination of SOF and DCS in pharmaceutical formulations and biological fluids based on coupling liquid-liquid extraction with ultrasound and dual wavelength detection at λ max ; 260 and 313 nm for SOF and DCS, respectively. This approach provided simple, sensitive, specific and cost-effective determination of the SOF-DCS mixture with good recoveries of the analytes from plasma. Analytes were separated within 7 min on C 18 analytical column with acetonitrile-10 mM acetate buffer of pH 5.0 at a flow rate of 1.0 mL min -1 . The linear ranges were 1-20 μg mL -1 for SOF and 0.6-6 μg mL -1 for DCS with correlation coefficients ≥0.9995. The detection limits in spiked rabbit plasma were 0.20 and 0.19 μg mL -1 for SOF and DCS, respectively. The method was validated according to ICH and US-FDA guidelines. Finally, the method was successfully applied for simultaneous pharmacokinetic studies of SOF and DCS in rabbits using rofecoxib as internal standard., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Sofosbuvir (SOF) and ledipasvir (LDS) represent anti-hepatitis C binary mixture. Herein, a fast high-performance thin-layer chromatography (HPTLC) method was developed, validated and applied for simultaneous determination of SOF and LDS in biological matrix. An innovative strategy was designed which based on coupling dual wavelength detection with HPTLC. This strategy enabled sensitive, specific, high sample throughput and cost-effective determination of the SOF-LDS binary mixture. The developed HPTLC procedure is based on a simple liquid-liquid extraction, enrichment of the analytes and subsequent separation with UV detection. Separations were performed on HPTLC silica gel 60 F 254 aluminum plates with a mobile phase consisting of ethyl acetate-glacial acetic acid (100:5, v/v). The R f values for SOF and LDS were 0.62 and 0.30, respectively. Dual wavelength scanning was carried out in the absorbance mode at 265 and 327 nm for SOF and LDS, respectively. The linear ranges were 40-640 and 9-144 ng/band for SOF and LDS, respectively with correlation coefficients of 0.9998. The detection limits were 10.61 and 2.54 ng/band and the quantitation limits were 32.14 and 7.70 ng/band for SOF and LDS, respectively indicating high sensitivity of the proposed method. Consequently, this permits in vitro and in vivo application of the proposed method in rabbit plasma with good percentage recovery (95.68-103.26%). Validation parameters were assessed according to ICH guidelines. The proposed method represents a simple, high sample throughput and economic alternative to the already existing more complicated reported LC-MS/MS techniques. The method would afford an efficient tool for therapeutic drug monitoring and bioavailability studies of SOF and LDS., (Copyright © 2018 Elsevier B.V. All rights reserved.)

A rapid, simple, selective and precise fluorimetric method was developed and validated for determination of a selective xanthine oxidase inhibitor; febuxostat (FBX) in pharmaceutical formulations and in human plasma. The proposed method is based on quenching effect of FBX on the fluorescence intensity of terbium (Tb 3+ ) through fluorescence resonance energy transfer (FRET) from Tb 3+ to FBX. The formed complex was measured at λ ex. 320 nm/λ em. 490 nm against a reagent blank. Fluorescence intensity of Tb 3+ was diminished when FBX was added. A linear relationship between the fluorescence quenching value of the formed complex ΔF=FTb3+-FFBX-Tb3+ and the concentration of FBX was investigated. The reaction conditions and the fluorescence spectral properties of the complex have been studied. The linearity range of the developed method was 1.0-16.0 μg/ml. The suggested method was applied successfully for the estimation of FBX in bulk powder, dosage forms and spiked plasma samples with excellent recoveries (96.79-98.89%). In addition, the developed method has been successfully applied for determination of FBX in real plasma samples collected from healthy volunteers with good recoveries (82.06-85.65%). All obtained results of the developed method were statistically analyzed and validated according to ICH (International Conference on Harmonization) guidelines., (Copyright © 2018 John Wiley & Sons, Ltd.)

Sofosbuvir (SOF) and daclatasvir (DCS) are newly discovered anti-hepatitis C drugs that have direct antiviral activity. A novel and simple high-performance thin-layer chromatography (HPTLC) method was designed for simultaneous determination of SOF and DCS in miscellaneous matrices. The method adopts coupling HPTLC with dual wavelength spectrodensitometry. Consequently, this enabled sensitive, specific and cost-effective determination of the SOF-DCS mixture. The developed HPTLC procedure is based on a simple liquid-liquid extraction, enrichment of the analytes and subsequent chromatographic separation with UV detection. Separations were performed on HPTLC silica gel 60 F 254 aluminum plates with a mobile phase consisting of ethyl acetate-isopropanol (85:15, v/v). Dual wavelength scanning was carried out in the absorbance mode at 265 and 311 nm for SOF and DCS, respectively. The linear ranges were 40-640 and 20-320 ng band -1 for SOF and DCS, respectively with correlation coefficients of ≥0.9997. The detection limits were 11.3 and 6.5 ng band -1 for SOF and DCS, respectively indicating high sensitivity of the proposed method. Consequently, this permits in vitro and in vivo application of the proposed method in human plasma with good percentage recovery (94.1-103.5%). Validation parameters were assessed according to ICH guidelines and US-FDA guidelines. Furthermore, the application was extended to analysis of SOF and DCS in their pharmaceutical formulations., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Direct-acting antivirals (DAAs) represent a revolution in the treatment of chronic hepatitis C which have emerged at an extremely rapid pace over the past few years. DAAs act directly on the hepatitis C virus at various points in the viral life cycle to inhibit viral production. Among these novel DAAs, are daclatasvir (DCS) and ledipasvir (LDS). Herein, a novel, fast, simple, ultrasensitive and cost-effective spectrofluorimetric method was designed for determination of DCS and LDS in miscellaneous matrices. The method is based on investigation of the native fluorescence of the cited drugs. The relative fluorescence intensity (RFI) was measured at λ ex /λ em equal to 315/381 nm for DCS and 332/387 nm for LDS. Under the optimum conditions, the linear ranges of calibration curves were 0.2-30 and 6-120 ng mL -1 for DCS and LDS, respectively with correlation coefficients ≥0.9998. The detection limits were 0.047 and 1.939 ng mL -1 for DCS and LDS, respectively indicating ultrasensitivity of the proposed method. Consequently, this permits in vitro and in vivo application of the proposed method in spiked and real human plasma with good percentage recovery (96.6-103.6%). The method was validated in compliance with ICH guidelines and US-FDA guidelines. Furthermore, the application was extended to analysis of DCS and LDS in its pharmaceutical formulations (either alone or in presence of other co-formulated drugs) and in synthetic mixture with sofosbuvir or ribavirin., (Copyright © 2018 Elsevier B.V. All rights reserved.)

A validated simple, novel, and rapid spectrofluorimetric method was developed for the determination of some non-sedating antihistamines (NSAs); namely cetirizine (CTZ), ebastine (EBS), fexofenadine (FXD), and loratadine (LOR). The method is based on measuring the native fluorescence of the cited drugs after protonation in acidic media and studying their quantitative fluorescence intensity - structure relationships. There was a linear relationship between the relative fluorescence intensity and the concentration of the investigated drug. Under the optimal conditions, the linear ranges of calibration curves for the determination of the studied NSAs were 0.10-2.0, 0.20-6.0, and 0.02-1.0 [Formula: see text] for (CTZ, FXD), (EBS), and (LOR); respectively. The factors affecting the protonation of the studied drugs were carefully studied and optimized. The method was validated according to ICH guidelines. The suggested method is applicable for the determination of the four investigated drugs in bulk and pharmaceutical dosage forms with excellent recoveries (97.67-103.80%). Quantitative relationships were found between the relative fluorescence intensities of the protonated drugs and their physicochemical parameters namely: the pKa, log P, connectivity indexes (χ(v)) and their squares. Regression equations (76) were obtained and not previously reported. Six of these equations were highly significant and used for the prediction of RFI of the studied NSAs.

The combination of certain non-sedating antihistamines (NSA) such as fexofenadine (FXD), ketotifen (KET) and loratadine (LOR) with pseudoephedrine (PSE) or acetaminophen (ACE) is widely used in the treatment of allergic rhinitis, conjunctivitis and chronic urticaria. A rapid, simple, selective and precise densitometric method was developed and validated for simultaneous estimation of six synthetic binary mixtures and their pharmaceutical dosage forms. The method employed thin layer chromatography aluminum plates precoated with silica gel G 60 F254 as the stationary phase. The mobile phases chosen for development gave compact bands for the mixtures FXD-PSE (I), KET-PSE (II), LOR-PSE (III), FXD-ACE (IV), KET-ACE (V) and LOR-ACE (VI) [Retardation factor (Rf ) values were (0.20, 0.32), (0.69, 0.34), (0.79, 0.13), (0.36, 0.70), (0.51, 0.30) and (0.76, 0.26), respectively]. Spectrodensitometric scanning integration was performed at 217, 218, 218, 233, 272 and 251 nm for the mixtures I-VI, respectively. The linear regression data for the calibration plots showed an excellent linear relationship. The method was validated for precision, accuracy, robustness and recovery. Limits of detection and quantitation were calculated. Statistical analysis proved that the method is reproducible and selective for the simultaneous estimation of these binary mixtures., (Copyright © 2013 John Wiley & Sons, Ltd.)

The stability of adriamycin (ADR), adriamycinol, adriamycinone (ADR-ONE) and daunomycin in the presence of alpha-, beta- and gamma-cyclodextrins (CDs) was studied using high-performance liquid chromatography. It was found that alpha-CD did not affect the degradation of tested compounds, beta-CD caused a little effect and gamma-CD resulted in pronounced stabilizing effect. The formation of complexes between ADR and ADR-ONE with CDs was monitored by fluorescence spectroscopy. The fluorescence spectrum of ADR-gamma-CD complex had an activation maximum at 460 nm, emission maximum at 555 nm and a shoulder at 585 nm. A similar finding was observed in case of alpha-CD. In case of beta-CD, the fluorescence intensity at 580 nm peak enhanced less than in case of gamma-CD. With ADR-ONE, alpha-CD did not cause any significant change compared with the spectrum of free molecule. On the other hand, it was noticed that, the fluorescence spectra of ADR-ONE with both beta- and gamma-CD were the same but showed a significant difference to the spectrum of free molecule, especially the molar fluorescence of the 585 nm emission peak.

Adriamycin, adriamycinol, adriamycinone and duanorubicin were simultaneously determined by the development of an on-line plasma clean-up system. A short protein-coated Lichrosorb, RP-8, RP-2, CN and muBondapak phenyl as well as ODS silica have been examined for their performance as pre-columns. The drugs and metabolites were separated from weakly retained plasma components through two steps; phosphate buffer saline, pH 7.4 and 15% acetonitrile in 0.1 M sodium dihydrogen phosphate, pH 3. The chromatographic conditions were: ODS/TM column, flow rate 1 ml/min, 35% acctonitrile in 0.1 M sodium dihydrogen phosphate (pH 3) containing 0.3% heptafluorobutyric acid as mobile phase. The detection was carried out using fluorescence monitor operated at an emission 555 nm and excitation 460 nm. Good resolution was obtained within 13 min. This method is reproducible for analysis of drugs and metabolites (99.3-100.1%, CV < 2%) in plasma.

A novel high performance liquid chromatographic method (HPLC) is presented for the quantitative determination of piroxicam in capsule formulation (Feldene capsule). Samples are separated on a chemically bonded beta-cyclodextrin column (Cyclobond I) with a mobile phase of 75% 0.05M phosphate buffer (pH 7.0) and 25% methanol. The effluent is monitored by a spectrophotometric detector with a 254-nm filter. The method is rapid, accurate, and precise.