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Gout is one of the most prevalent forms of arthritis that is usually accompanied by other comorbidities. For this reason, multiple drugs are routinely prescribed for gout patients, which may affect the clinical course outcomes, and increase the risk of drug-drug interactions. This work presents a novel, simple, and sensitive high performance liquid chromatography (HPLC) method for the simultaneous determination of lesinurad (LES) and other co-administered drugs that are subject to potential pharmacokinetic interactions such as etoricoxib (ETC), eplerenone (EPL), and amiodarone (AMD) in rat plasma. Moreover, a pharmacokinetic study was conducted by co-administration of LES and ETC to rats to assess any possible alteration in their pharmacokinetic profiles and the obtained samples were analyzed using the developed method. Chromatographic separation was achieved using a gradient elution of a mobile phase consisting of acetonitrile and potassium dihydrogen orthophosphate buffer, pH 4.2 on a Zorbax Eclipse Plus C18 (4.6 × 250 mm, 5 μm particle size) column. The developed method exhibits adequate sensitivity with a LLOQ of 100 ng/mL and was successfully validated as per the FDA bioanalytical guidelines and was found to be linear over the range from 100 to 50,000 ng/mL for all the selected drugs. The results of the pharmacokinetic study showed an increase in the area under the curve (AUC) of each of the two drugs (LES and ETC) following the repeated administration of the other. This raises concerns of the possible renal injurious effect of ETC when co-prescribed with LES. Moreover, this work uncovers the necessity for therapeutic dose adjustment or increased clinical vigilance for side effects and/or lack of efficacy upon concomitant administration of the selected drugs to gout patients.

Nitazoxanide (NTX) is an antimicrobial drug that was used for the treatment of various protozoa. However, during the coronavirus pandemic, NTX has been redirected for the treatment of such virus that primarily infect the respiratory tract system. NTX is now used as a broad-spectrum antiviral agent. In this study, a highly sensitive and green spectrofluorometric method was developed to detect NTX in various dosage forms and its metabolite, tizoxanide (TX), in human plasma samples using nitrogen and sulfur co-doped carbon quantum dots nanosensors (C-dots). A simple and eco-friendly hydrothermal method was used to synthetize water soluble C-dots from citric acid and l-cysteine. After excitation at 345 nm, the luminescence intensity was measured at 416 nm. Quenching of C-dots luminescence occurred upon the addition of NTX and was proportional to NTX concentration. Assessment of the quenching mechanism was performed to prove that inner filter effect is the underlying molecular mechanism of NTX quenching accomplished. After optimizing all experimental parameters, the analytical procedure was evaluated and validated using the ICH guidelines. The method linearity, detection and quantification limits of NTX were 15 × 10 –3 –15.00 µg/mL, 56.00 × 10 –4 and 15 × 10 –3 µg/mL, respectively. The proposed method was applied for the determination of NTX in its commercial pharmaceutical products; Nanazoxid ® oral suspension and tablets. The obtained % recovery, relative standard deviation and % relative error were satisfactory. Comparison with other reported spectrofluorimetric methods revealed the superior sensitivity of the proposed method. Such high sensitivity permitted the selective determination of TX, the main metabolite of NTX, in human plasma samples making this study the first spectrofluorimetric method in literature that determine TX in human plasma samples. Moreover, the method greenness was assessed using both Eco-Scale and AGREE approaches to prove the superiority of the proposed method greenness over other previously published spectrofluorimetric methods for the analysis of NTX and its metabolite, TX, in various dosage forms and in human plasma samples.

Four simple, sensitive, economical, and eco-friendly spectrophotometric and spectrofluorimetric methods for the assay of erdosteine (ERD) in bulk and dosage form have been developed and validated as per the current ICH guidelines. Method I involved the addition of the powerful oxidizing agent, potassium permanganate to ERD and measuring the oxidation product at 600 nm. Another oxidizing agent; ceric ammonium sulfate was used in Method II where ERD is oxidized resulting in a decline in the absorbance intensity of cerium (IV) ions, measured at 320 nm. Similarly, Method III employed the use of ceric ammonium sulfate, However, the fluorescence intensity of the resulting cerium (III) ions was recorded at λex/λem 255/355 nm, respectively. Whereas in Method IV, ERD was added to acriflavine leading to a proportional decrease in its native fluorescence. Various reaction conditions affecting the intensity of measurement were attentively investigated, optimized, and validated. All the suggested methods did not require any tedious extraction procedures nor organic solvents. The implementation of the proposed methods in ERD assay resulted in linear relationships between the measured signals and the corresponding concentrations of ERD in the range of 1–6, 0.1–1.0, 0.01–0.1, and 10–100 μg/mL with LOD values 0.179, 0.024, 0.0027 and, 3.2 μg/mL for methods I, II, III and IV respectively. The suggested methods were successfully applied to ERD analysis in pure form and in commercial capsules. Furthermore, the eco-friendliness of the proposed methods was thoroughly checked using various greenness testing tools. Lastly, this work, not only presents highly sensitive, green, mix-and-read methods for ERD determination, but also, describes the determination of ERD spectrofluorimetrically for the first time in the literature.

In this article, a new series of 2-((3,5-disubstituted-2-thioxo-imidazol-1-yl)imino)acenaphthylen-1(2 )-ones were synthesized. Imidazole-2-thione with acenaphthylen-one gave a hybrid scaffold that integrated key structural elements essential for DNA damage direct DNA intercalation and inhibition of the topoisomerase II enzyme. All the synthesized compounds were screened to detect their DNA damage using a terbium fluorescent probe. Results demonstrated that 4-phenyl-imidazoles and in addition to 4-(4-chlorophenyl)imidazoles and would induce detectable potent damage in ctDNA. The four most potent compounds as DNA intercalators were further evaluated for their antiproliferative activity against HepG2, MCF-7 and HCT-116 utilizing the MTT assay. The highest anticancer activity was recorded with compounds and against the breast cancer cell line MCF-7 which were 1.5- and 3- folds more active than , respectively. Therefore, imidazole-2-thione tethered acenaphthylenone derivatives can be considered as promising scaffold for the development of effective dual DNA intercalators and topoisomerase II inhibitors.

A series of triazole-tethered triazines bearing pharmacophoric features of DNA-targeting agents and non-hydroxamate MMPs inhibitors were synthesized and screened against HCT-116, Caco-2 cells, and normal colonocytes by MTT assay. and surpassed doxorubicin against HCT-116 cells regarding potency (IC = 0.87 and 1.41 nM) and safety (SI = 181.93 and 54.41). was potent against liver cancer (HepG-2; IC = 65.08 nM), the main metastatic site of CRC with correlation to MMP-13 expression. Both derivatives induced DNA damage at 2.67 and 1.87 nM, disrupted HCT-116 cell cycle and triggered apoptosis by 33.17% compared to doxorubicin (DNA damage at 0.76 nM and 40.21% apoptosis induction). surpassed NNGH against MMP-10 (IC = 0.205 μM) and MMP-13 (IC = 0.275 μM) and downregulated HCT-116 VEGF related to CRC progression by 38%. Docking and MDs simulated ligands-receptors binding modes and highlighted SAR. Their ADMET profiles, drug-likeness and possible off-targets were computationally predicted.

Over the recent years, there has been a notable surge in consumer demand for rapid and effective weight-loss pharmaceuticals that are also capable of managing type 2 diabetes. Owing to their exceptional efficacy, GLP-1 receptor agonists, including Tirzepatide (TIR) and Semaglutide (SEM), have had phenomenal outcomes and confidence among consumers. A rapid, straightforward, and thorough approach for quantifying SEM and TIR is essential for quality control purposes given the rising use of these drugs in the pharmaceutical industry. This work presents the first stability-indicating HPLC method for quantifying TIR and SEM under various stress conditions (acidic and basic hydrolysis, oxidative, and photolytic degradation) without interference from degradants. In addition, the proposed methods are capable of accurately quantifying each drug in bulk, pharmaceutical dosage forms, and spiked plasma. The analysis of TIR and SEM was performed using an Inertsil ODS-3 (4.6 × 250 mm, 5 μm particle size) C18 column and the elution of the drugs was achieved isocratically using 0.1% formic acid (pH 2.5) and ACN in the ratio 30:70 with a flow rate 1 mL/min using DAD detector at 220 nm with SEM and TIR eluting at 1.42 and 1.68 min respectively. The proposed method was validated in line with the International Conference of Harmonization (ICH) guidelines and has demonstrated excellent accuracy, linearity, and superior sensitivity with LOD values of 10 and 16 ng/mL for TIR and for SEM, respectively. The obtained linearity range for both TIR and SEM was 1–500 µg/mL with correlation coefficients > 0.9999. An in-depth six- edged sustainability assessment of the proposed method was conducted using greenness, whiteness, blueness and violet innovation metrics was performed using Analytical Greenness Metric (AGREE), Modified Green Analytical Procedure Index (MoGAPI), Analytical Eco-scale, Analytical Green Star Area (AGSA), Carbon Footprint Reduction Index (CaFRI), Whiteness using RGB algorithm, Blue Applicability Grade Index (BAGI), Click Analytical Chemistry Index (CACI), Violet Innovation Grade Index (VIGI) tools and Stability Toolkit for the Appraisal of Bio/Pharmaceuticals’ Level of Endurance (STABLE).

The development of two eco-friendly analytical methods for the simultaneous determination of eight cardiovascular drugs; hydrochlorothiazide (HCT), captopril (CPL), lisinopril (LSP), valsartan (VAL), atorvastatin (ATR), bisoprolol (BSL), amlodipine (AML) and carvedilol (CVL); alongside with the nutraceutical vincamine (VIC) is essential for sustainable pharmaceutical analysis. This study explores the application of Micellar Electro Kinetic Chromatography (MEKC) and High-Performance Liquid Chromatography (HPLC) for this purpose. In MEKC method, the separation was done using fused silica capillary (41.5 cm × 50 µm id) and a back ground electrolyte consisting of 50 mM borate buffer (pH 9) containing 50 mM sodium lauryl sulphate (SLS) and 10% organic modifier (Acetonitrile). In HPLC method, separation was performed on a ZORBAX Extend-C18 (4.6 × 250 mm, 5 µm) column, using a gradient mobile phase consisting of 50 mM phosphate buffer pH 3 and methanol. Both methods attained good linearity (r ≥ 0.9996) with low values of LOD and LOQ. Both methods were successfully applied in the determination of co-administered single, binary and ternary dosage form of the studied drugs. Moreover, application of various combinations of co-administered dosage forms was achieved in rat plasma, confirming the applicability of these methods in different matrices. The use of micellar solutions in MEKC enhances separation efficiency while reducing the need for organic solvents, aligning with green chemistry principles. HPLC methods were optimized using environmentally benign solvents, ensuring reduced toxicity and waste production. The methodologies were evaluated through green, white, and blue metrics to ensure comprehensive sustainability, considering ecological impact, safety, and practical efficiency. These methods were not only cost-effective and time-saving but achieved high efficiency, sensitivity, and reproducibility making them ideal for routine use in pharmaceutical analysis.

Keratomycosis, a sight-threatening fungal infection of the cornea, can be more effectively treated with a novel combination of Natamycin (NAT, 5%) and Fluconazole (FLC, 0.2%) than with NAT alone. To support the development of this therapy, new sustainable, eco-friendly, and sensitive analytical methods were developed for the simultaneous quantification of both drugs in pharmaceutical formulations. Two techniques were successfully employed. The first was a Reversed-Phase High-Performance Liquid Chromatography (RP-HPLC) method using an isocratic mobile phase of methanol and water (70:30%v/v) at a 1 mL/min flow rate. Detection was accomplished with both diode array (DAD) and fluorescence (FLD) detectors. The second technique was a Capillary Zone Electrophoresis (CZE) method utilizing a capillary (56 cm effective length, 50 μm internal diameter) at ambient temperature. Samples were injected hydrodynamically at 50 mbar pressure. The environmental sustainability and practical applicability of these methods were rigorously evaluated using modern assessment tools: the Greenness, Whiteness, and Blueness approaches. Furthermore, their innovative character was formally quantified using a novel metric, the Violet Innovation Grade Index (VIGI).

Background Tigecycline (TIG), an antimicrobial agent indicated for complex bacterial infections, is now approved by FDA as an orphan chemotherapeutic agent for the treatment of acute myeloid leukemia due to its inhibitory effects on pathways of activating, signaling and abnormal mitochondrial function in cancer cells. TIG is mainly administered as intravenous infusion through centralized unit of oncology centers. This necessitates the continuous analytical quality control of the prepared solution in order to identify and quantify TIG for safe intravenous administration to patients. Moreover, the clinical staff exposure risk to toxic drugs during daily handling must be considered. Such concerns require a fast, cost-effective and green analytical procedure for sensitive determination of TIG directly in infusion bags. In this work, we propose a simple, rapid and green capillary zone electrophoretic (CZE) method for the sensitive assay of TIG directly in infusion bags, in addition to three simple and green spectrophotometric methods. Results TIG solutions corresponding to clinical ranges were detected in 5%glucose. Validation of all the proposed methods was according to ICH guidelines. Greenness assessment was performed depending on Green Analytical Procedure Index (GAPI) and the Eco-scale approach which showed that the proposed methods are better eco-friendly methods than reported ones. It also revealed the superiority of our proposed methods in terms of simplicity and sensitivity for TIG determination in infusion bags. Quantification limits obtained were significantly lower than the administered range of TIG in infusion bags and lower than its maximum serum concentration ( C max ). This promotes the application of the proposed methods for the pharmacokinetics and bioavailability studies of TIG in various biological fluids. Conclusions This work reports, for the first time, CZE method for the direct and rapid determination of TIG and its separation from other components in intravenous infusion solution. The developed CZE method has several advantages over current chromatographic methods such as higher efficiency of separation within short analysis time, consumption of fewer quantities of chemicals and offering better resolution than HPLC. Moreover, three green spectrophotometric methods are also proposed for TIG determination that offer many advantages such as accuracy, precision, simplicity, specificity and facility of quantification and separation of the selected drug in infusion bags and pharmaceutical preparations without any techniques for extraction.

Green analytical chemistry is one of the newest trends in analytical chemistry nowadays targeting the concept of green laboratory practices on chemists and environment. In this text, green practices are proposed in this work for the determination of sofosbuvir (SF) and velpatasvir (VP) in their pharmaceutical formulation. The analysis of SF in a binary mixture with VP represents an analytical challenge due to the complete overlapping of the UV spectrum of SF by that of VP. Therefore, the direct absorbance and derivative measurements cannot resolve such interference and failed to determine SF. In this paper, three direct and simple methods were developed for the analysis of SF without any interference from VP without sample pre-treatment. The proposed methods include measuring the second derivative amplitude of the ratio spectrum of the mixture using VP as a divisor, measuring the absorbance difference of the mixture in NaOH solution against its HCl solution, and using the derivative compensation technique. On the other hand, VP was determined specifically in presence of SF by two methods. Firstly, by its reaction with 4-chloro-7-nitrobenzofurazan (NBD-Cl) where the reaction product was measured spectrophotometrically and spectrofluorometrically and secondly through the reaction of VP with 3-methyl-2-benzothiazolinone hydrazone hydrochloride (MBTH). The calibration curves showed good correlation coefficient (r2 > 0.999). The developed methods were highly precise with RSD% values less than 2%. The method greenness profile was compared with other published methods by applying the eco-scale protocol. Assessment results proved that our analytical procedure is greener than other reported methods. Moreover, upon comparison with other methods, the proposed methods showed better or comparable sensitivity in addition to being inexpensive and ecofriendly. Accordingly, these methods could be readily applied for quality control purposes as an eco-friendly, simple and efficient analytical tool.