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On-site, robust, and quantitative detection of diclofenac (DCF) is highly significant in bioanalysis and quality control. Fluorescence-based metal-organic frameworks (MOFs) play a pivotal role in biochemical sensing, offering a versatile platform for detecting various biomolecules. However, conventional fluorescent MOF sensors often rely on lanthanide metals, which can pose challenges in terms of cost, accessibility, and environmental impact. Herein, an intrinsic blue fluorescent zinc-based metal-organic framework (FMOF-5) was prepared free from lanthanide metals. Coordination-induced emission as an effective strategy was followed wherein a non-fluorescent ligand is converted to a fluorescent one after insertion in a framework. Conventional fluorometry and smartphone-assisted visual methods were employed for the detection of DCF. The fluorescence emission of the FMOF-5 was effectively quenched upon the addition of the DCF, endowing it an "off" condition, which permits the construction of a calibration curve with a wide linear range of 30-670 µM and a detection limit of about 4.1 µM. Other analytical figures of merit, such as linearity, sensitivity, selectivity, accuracy, and precision were studied and calculated. Furthermore, the proposed sensor was successfully applied to quantify DCF in pharmaceutical tablets with reliable recovery and precision. Importantly, the elimination of lanthanide metals from the fluorescence detection system enhances its practicality and sustainability, making it a promising alternative for DCF detection in pharmaceutical analysis applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The identification and quantification of melatonin (MT) are crucial for early diagnosis of disorders associated with circadian rhythm disruption. Herein, novel blue-emissive carbon dots (BCDs) were synthesized through an improved hydrothermal treatment using serine and malic acid as reductant and carbon source. The excellent optical properties of the as-obtained BCDs were used for ratiometric sensing by strategically constructing a MT sensing system integrating BCDs with C 3 N 4 nanosheets loaded with platinum/ruthenium nanoparticles (PtRu/CN). In this system, H 2 O 2 activated the peroxidase-like activity of PtRu/CN to generate •OH and 1 O 2 for oxidizing the colorless o-phenylenediamine (OPD) into yellow 2,3-diaminophenazine (DAP) with fluorescence emission at 565 nm. Concurrently, the fluorescence emission of BCDs at 439 nm was quenched by the generated DAP via the static quenching and inner filter effect (IFE) process. However, MT rapidly scavenged the generated free radicals to reverse the ratio fluorescence signal. The developed BCDs/PtRu/CN/OPD/H 2 O 2 sensing platform enabled quantitative analysis of MT at concentrations ranging from 0.06 to 600 μmol/L with a low detection limit of 23.56 nmol/L. Moreover, smartphone-based RGB sensing of MT was successfully developed for rapid visualization and portable processing. More broadly, novel insights into the preparation of carbon dots with sensitive fluorescence sensing properties were presented, promising for future considerations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Novel methods were proposed for determining primaquine (PQN) in tablets by multiple-injection capillary zone electrophoresis (MI-CZE) and by short-end injection CZE (SEI-CZE), both with ultraviolet detection. The background electrolyte (BGE), consisting of 20 mmol/L of tris (hydroxymethyl) aminomethane and 30 mmol/L of hydrochloric acid at pH 2.0, was selected considering a comprehensive study involving the effective mobility versus pH curves of the analytes and BGE components. Experimental designs were applied in methods developments, showing the chemometric tool's applicability in achieving suitable electrophoretic conditions. A baseline resolution in the separation of adjacent peak pairs was obtained by injecting a spacer electrolyte for 18 s, with a voltage of + 15 kV, and the sample can be injected six consecutive times in a single run in less than 3 min, in the MI-CZE method. For the SEI-CZE method, the migration time of PQN was 0.6 min, and the method was applied to a demonstrative forced degradation study. Some validation parameters were evaluated for both methods, and all results were satisfactory, indicating that they can be implemented as PQN determination methods in routine quality control analyses., (© 2024 Wiley‐VCH GmbH.)

A simple, specific, sensitive, rapid, and cost-effective spectrofluorometric method for quantifying folic acid has been developed using basic fuchsin as a fluorescence quenching agent. This method relies on the quenching effect of folic acid on the inherent fluorescence of basic fuchsin, facilitated by their interaction in Britton-Robinson buffer solution at pH 9, leading to the formation of an ion-associated complex. The decrease in fluorescence intensity of basic fuchsin was measured at 730 nm, with excitation at 365 nm. The method demonstrated a linear relationship (R 2  = 0.9977) between the quenching fluorescence intensity (ΔF) and folic acid concentration over the range of 4-20 μg/mL, with a detection limit of 0.17 μg/mL. The method showed no significant interference from common excipients found in pharmaceutical tablets. The results obtained were in good agreement with those from high-performance liquid chromatography, with no significant differences in precision or accuracy. This spectrofluorimetric method was successfully applied to determine the folic acid content in various commercial pharmaceutical tablets., (© 2024 John Wiley & Sons, Ltd.)

The synthesis and characterization of pH-sensitive boron and nitrogen co-doped CDs (B, N-CDs) is reported. The fluorescence of B, N-CDs exhibited pH-responsive behavior within the range pH 3.0-6.0, attributed to their controlled aggregation and disaggregation. Interestingly, the fluorescence of B, N-CDs was quenched by the inner filter effect from chrome azurol S (CAS). With the subsequent addition of Al 3+ , the fluorescence of B, N-CDs was restored due to the formation of blue Al 3+ -CAS and B, N-CDs-Al 3+ complexes. Consequently, a fluorescent and colorimetric dual-mode sensor for Al 3+ detection was developed. The proposed sensor enabled Al 3+ detection in the ranges and limits of detection of 3.75-22.5 μM and 2.67 μM for the fluorescent mode and 5-20 μM and 4.8 μM for the colorimetric mode, respectively. Furthermore, the efficacy of the sensor was validated through successful detection of Al 3+ in tablet samples. The obtained B, N-CDs promised the application in acid condition and the proposed sensor is expected to be applied to in situ on-line detection of Al 3+ ., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

In this study, a new magnetic solid phase extraction based on magnetic composite modified with biochar obtained from pumpkin peel was developed for the enrichment and extraction of Naproxen in lake water, tablet and urine samples. The effects of main parameters such as pH, extraction time, amount of adsorbent and sample volume, which affect magnetic solid phase extraction, were investigated. Under optimal conditions, intraday and interday precision values for naproxen were below 5.9, with accuracy (relative error) better than 7.0 %. The detection limit and preliminary concentration factor were 12 ng/mL and 10, respectively. The method proposed here can be used for routine analysis of naproxen in lake water, urine and tablets., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The simultaneous detection of multiple analytes through a single fluorescence sensor is highly attractive. In this study, phosphorus-doped graphitic carbon nitride quantum dots (P-CNQDs) were developed, achieving multi-mode sensing through three distinct response mechanisms. The preparation involved using melamine as the carbon and nitrogen source and ammonium dihydrogen phosphate as the phosphorus source. Uniform and narrowly distributed P-CNQDs were successfully synthesized through chemical oxidation and hydrothermal methods, with an average size of 2.4 nm. These unique P-CNQDs exhibited fluorescence quenching through photo-induced electron transfer (PET) in response to Ag + . Additionally, the formation of hydrogen bonds and coordination interactions between P-CNQDs-Ag + and ciprofloxacin (CIP) led to a pronounced fluorescence response to CIP by the chelation enhanced fluorescence (CHEF) mechanism. Furthermore, leveraging the principle of fluorescence resonance energy transfer (FRET), P-CNQDs-CIP served as a ratio fluorescence sensor for riboflavin (RF), enabling ultra-sensitive detection of RF. The combination of PET, CHEF, and FRET response mechanisms successfully facilitated multi-mode sensing for Ag + , CIP, and RF. The detection ranges were 0.05-100 μM, 0.002-2 μM, and 0.05-60 μM, with corresponding lowest detection limits of 17.1 nM, 1.1 nM, and 29.2 nM, respectively. This versatile sensor has been effectively applied to real samples, including the detection of river water and vitamin B 2 tablets., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Monitoring antipsychotic drugs in biological fluids, such as human serum and urine, is important for ensuring the safety and efficacy of psychiatric treatments. This process helps maintain therapeutic drug levels, minimize side effects, and optimize patient well-being. Chlorpromazine (CZ) is a widely prescribed antipsychotic drug used for conditions like schizophrenia, bipolar disorder, and acute psychosis. Almost all existing sensing techniques for CZ are either insensitive spectrophotometric methods or involve long and complex chromatographic procedures, limiting their routine use. In this work, we introduce a facile, green, and sensitive fluorimetric strategy with high reproducibility for detecting CZ in its pure form, tablet formulation, and spiked human plasma and urine without the need for derivatization reactions. The proposed method relies on the inhibition of the intramolecular photoinduced electron transfer (PET) effect by using 2.0 M acetic acid. This approach enables the linear detection of CZ from 3.0 to 600 ng/mL with remarkably low quantitation and detection limits of 1.51 and 0.49 ng/mL, respectively. Moreover, the developed method's greenness was evaluated., (© 2024 John Wiley & Sons Ltd.)

Aspartame is an artificial sweetener used in drinks and many foods. International Agency for Research on Cancer classified aspartame as possibly carcinogenic to humans (IARC Group 2B). In this study, a sensitive and selective spectrofluorimetric method was developed to detect aspartame. The method is based on switching on the fluorescence activity of aspartame upon its condensation with O-phthalaldehyde (Roth's reaction) in the presence of 2-mercaptoethanol. The reaction product was detected fluorometrically at λ em of 438 nm after λ ex of 340 nm. All reaction conditions required to yield the optimal fluorescence intensity were observed and investigated. Furthermore, the approach was validated according to ICH guidelines. Upon plotting the concentrations of aspartame against their associated fluorescence intensity values, the relationship between the two variables was linear within the range of 0.5-3.0 μg/mL. Furthermore, the method was employed to analyze the quantity of aspartame in commercial packages and soft drinks with an acceptable level of recovery. In addition, the Green Solvents Selecting Tool, Complementary Green Analytical Procedure Index, and the Analytical Greenness Metric tool were used to evaluate the sustainability and the greenness of the developed methodology., (© 2024 John Wiley & Sons Ltd.)

Parkinson's disease is a chronic, progressive neurological disease that currently affects about more than 10 million population worldwide. Rasagiline is a selective, irreversible monoamine oxidase type B inhibitor used as monotherapy in early Parkinson's disease. Rasagiline tablets have been recalled from market due to the presence of unacceptable levels of nitrosamine impurity. European Medical Agency has set up very stringent limit 100ng/day of N-nitrosorasagiline (NSRG) in drug product based on its mutagenicity. The analytical methods need to be sufficiently sensitive in order to adequately detect and quantify trace levels of NSRG. A highly sensitive LC-MS/MS method for determination of NSRG in rasagiline tablet formulation was developed by effectively separating on zorbax eclipse XDB C18 column using 0.1% formic acid in mixture of water and acetonitrile (35:65 v/v) in an isocratic mode at 0.5mL/min flow rate. The measurement of NSRG was performed using triple quadrupole mass detection accompanied by electrospray ionization in the multiple reaction monitoring mode. The validation of the method was comprehensive, demonstrating strong linearity across the concentration spectrum of 2 to 200ng/mL for NSRG. The obtained correlation coefficient exceeded 0.998, signifying a robust relationship. Recoveries spanning from 80.0% to 120.0% for NSRG were deemed satisfactory. The developed method was able to detect and quantitate NSRG at a concentration level of 1 to 2ng/mL respectively (1 to 2ppm with respect to 1mg/mL of rasagiline tablet sample concentration). The developed and validated method can be employed for routine quality control testing of rasagiline tablets., (Copyright © 2024 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

Portable near-infrared (NIR) spectrophotometers have emerged as valuable tools for identifying substandard and falsified pharmaceuticals (SFPs). Integration of these devices with chemometric and machine learning models enhances their ability to provide quantitative chemical insights. However, different NIR spectrophotometer models vary in resolution, sensitivity, and responses to environmental factors such as temperature and humidity, necessitating instrument-specific libraries that hinder the wider adoption of NIR technology. This study addresses these challenges and seeks to establish a robust approach to promote the use of NIR technology in post-market pharmaceutical analysis. We developed support vector machine and partial least squares regression models based on binary mixtures of lab-made ciprofloxacin and microcrystalline cellulose, then applied the models to ciprofloxacin dosage forms that were assayed with high performance liquid chromatography (HPLC). A receiver operating characteristic (ROC) analysis was performed to set spectrophotometer independent NIR metrics to evaluate ciprofloxacin dosage forms as "meets standard," "needs HPLC assay," or "fails standard." Over 200 ciprofloxacin tablets representing 50 different brands were evaluated using spectra acquired from three types of NIR spectrophotometer with 85% of the prediction agreeing with HPLC testing. This study shows that non-brand-specific predictive models can be applied across multiple spectrophotometers for rapid screening of the conformity of pharmaceutical active ingredients to regulatory standard., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

N-nitrosamines (NAs) are prevalent mutagenic impurities in various consumer products. Their discovery in valsartan-containing medicines in 2018 prompted global regulatory agencies to set guidelines on their presence and permissible levels in pharmaceuticals. In order to determine the NAs content in medicines, efficient and sensitive analytical methods have been developed based on mass spectrometry techniques. Direct analysis in real time-mass spectrometry (DART-MS) has emerged as a prominent ambient ionization technique for pharmaceutical analysis due to its high-throughput capability, simplicity, and minimal sample preparation requirements. Thus, in this study DART-MS was evaluated for the screening and quantification of NAs in medicines. DART-MS analyses were conducted in positive ion mode, for both direct tablet analysis and solution analysis. The analytical performance was evaluated regarding linearity, precision, accuracy, limits of detection, and quantification. The DART-MS proved to be suitable for the determination of NAs in medicines, whether through direct tablet analysis or solution analysis. The analytical performance demonstrated linearity in the range from 1.00 to 200.00 ng mL -1 , limits of quantification about 1.00 ng mL -1 , precision and accuracy lower than 15%, and no significant matrix effect for six drug-related NAs. In conclusion, the DART-MS technique demonstrated to be an alternative method to determine NAs in medicines, aligning with the principles of green chemistry.

Technical advances in the field of quality analysis allow an increasingly deeper look into the impurity profile of drugs. The ability to detect unexpected impurities in addition to known impurities ensures the supply of high-quality drugs and can prevent recalls due to the detection of harmful unexpected impurities, as has happened recently with the N-nitrosamine and azido impurities in losartan (LOS) drug products. In the present study, the LC-MS/HRMS approach described by Backer et al. was applied to an even more complex system, being the investigation of 35 LOS drug products and combination preparations purchased in 2018 and 2022 in German pharmacies. The film-coated tablets were analysed by means of four LC-MS/HRMS method variants. For the separation a Zorbax RR StableBond C18 column (3.0 ×100 mm, particle size of 3.5 µm, pore size of 80 Å), a gradient elution and for mass spectrometric detection a qTOF mass spectrometer with electrospray ionization in positive and negative mode was used. An information-dependent acquisition method was applied for the acquisition of high-resolution mass spectrometry data. The combination of an untargeted and a targeted screening approach revealed the finding of eight impurities in total. Beside the five LOS related compounds, LOS impurity F, J, K, L, M, and related compound D from amlodipine besilate, LOS azide and an unknown derivative thereof were detected. Identification and structure elucidation, respectively, were successfully performed using in silico fragmentation. Differences in the impurity profiles of drug products from 2018 and 2022 could be observed. This study shows that broad screening approaches like this are applicable to the analysis of drug products and can be an important enhancement of the quality assurance of medicinal products., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Laura Backer reports financial support was provided by Frankfurt Foundation Quality of Medicines. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The ability to determine the purity (% controlled compound) of drug-of-abuse samples is necessary for public health and law enforcement. Here, we describe the assessment of atmospheric solids analysis probe (ASAP) for the rapid determination of drug purity for a set of formulated pharmaceuticals, chosen due to their availability, uncontrolled status and consistency. Paracetamol and loratadine were used as models of high and low purity compounds being ~90% and ~10% active ingredient, respectively. Individual tablets were ground up and diluted in an internal standard solution. The resulting samples were analysed by ASAP coupled to a Waters QDa mass spectrometer followed by confirmatory testing by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The inclusion of a non-matched internal standard (quinine) improved linearity and repeatability of drug analysis by ASAP-MS. Levels of drug purity using formulated pharmaceutical tablets were found to be highly comparable with results produced by the 'gold standard' LC-MS/MS technique. Rapid determination of drug purity is therefore possible with ASAP-MS for highly concentrated samples with minimal sample preparation. It may be possible to use this deployable system to determine drug purity outside of a laboratory setting., (© 2023 The Authors. Drug Testing and Analysis published by John Wiley & Sons Ltd.)

This work introduces an innovative gold-leaf flow cell for electrochemical detection in flow injection (FI) analysis. The flow cell incorporates a hammered custom gold leaf electrochemical sensor. Hammered gold leaves consist of pure gold and are readily available in Thailand at affordable prices (approximately $0.085 for a sheet measuring 40 mm × 40 mm). Four sensing devices can be made from a single sheet of this gold leaf, resulting in a production cost of approximately $0.19 per sensor. Each electrochemical sensor has the gold leaf as the working electrode, together with a printed carbon strip, and a printed silver/silver chloride strip as the counter and reference electrodes, respectively. Initial investigations using cyclic voltammetry of a standard 1000 μmol L⁻ 1 iodide solution in 60 mmol L⁻ 1 phosphate buffer (PB) solution at pH 5, demonstrated performance comparable to that of a commercial screen-printed gold electrode. The hammered gold leaf electrode was then installed in a commercial flow cell as part of an FI system. A sample or standard iodide solution (100 μL) is injected into the first carrier stream of phosphate buffer (PB) solution, which then merges to mix with the second stream of the same buffer solution before flowing into the flow cell for amperometric detection of iodide. The optimized operating conditions include a fixed potential of +0.39 V (vs Ag/AgCl), and a total flow rate of 3 mL min⁻ 1 . A linear calibration is obtained in the concentration range of 1 to 1000 μmol L⁻ 1 I - with a typical equation of μA = (0.00299 ± 0.00004) × (μmol L -1 I - ) + (0.021 ± 0.020), and R 2  = 0.9994. Analysis of iodide using this gold leaf-FI system is rapid with sample throughput of 86 samples h⁻ 1 and %RSD of a sample of 100 μmol L⁻ 1 I⁻ of 1.2 (n = 29). The limit of detection, (calculated as 2.78 × SD of regression line/slope), is 27 μmol L⁻ 1 I - . This method was successfully applied to determine iodide in nuclear emergency tablets., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

In this work, a highly sensitive and selective method for detecting folic acid (FA) was developed using D-penicillamine (DPA) stabilized Ag/Cu alloy nanoclusters (DPA@Ag/Cu NCs). The yellow emission of DPA@Ag/Cu NCs was found to be quenched upon the addition of FA to the system. The fluorescence intensity quenching value demonstrated a linear relationship with FA concentrations ranging from 0.01 to 1200 μM, with a limit of detection (LOD) of 5.3 nM. Furthermore, the detection mechanism was investigated through various characterization analyses, including high resolution transmission electron microscopy, fluorescence spectra, ultraviolet-visible absorption spectra, and fluorescence lifetime. The results indicated that the fluorescence quenching induced by FA was a result of electron transfer from FA to the ligands of DPA@Ag/Cu NCs. The selectivity of the FA sensor was also evaluated, showing that common amino acids and inorganic ions had minimal impact on the detection of FA. Moreover, the standard addition method was successfully applied to detect FA in human serum, chewable tablets and FA tablets with promising results. The use of DPA@Ag/Cu NCs demonstrates significant potential for detecting FA in complex biological samples., (© 2024 Wiley-VCH GmbH.)

A recently developed antipsychotic drug, lurasidone, was determined using a simple, sensitive, and eco-friendly spectrofluorimetric approach. The suggested approach was based on the quantifiable quenching impact of lurasidone on the inherent fluorescence of erythrosine B in an acidic environment employing a Teorell-Stenhagen buffer (pH 4). Following excitation at 530 nm, the quenching of erythrosine B fluorescence was monitored at 552 nm. The system variables were systematically optimized to enhance the formation of the lurasidone-erythrosine B ion pair for analytical purposes. A linear calibration graph was built in the range of 20-600 ng mL -1 with 0.9998 as a coefficient of correlation. The quantitation and detection limits were 13.5 and 4.5 ng/mL, respectively. The analytical validity of the designed approach was assessed with respect to International Council on Harmonization (ICH) guiding principles. The proposed methodology was employed with high recoveries for assessing lurasidone in bulk powder and its therapeutic tablet dosage form. Additionally, the uniformity of tablet formulations was tested using the developed approach. Finally, the established approach was assessed for its greenness using various tools., (© 2024 John Wiley & Sons Ltd.)

We report on the spectral selection of excitation wavelength towards selective detection of aluminum and iron ions using dual emission polymer carbon dots (PCDs). PCDs were prepared from glucose and dilute sulfuric acid using one-pot solvothermal method. The PCDs emit blue light at 480 nm when excited at 340 nm, while emit red light at 590 nm when excited with 400 nm. Spectral selection (selection of excited state) showed sensitivity enhancement for detection of some metal ions. The PCDs showed fluorescence enhancement when combined with Al3+ ions with hypsochromic shift centered at 470 nm when excited at 440 nm. While the PCDs selectively quenched via addition of Fe3+ ions, when excited at 400 nm. The wavelength selection of the same carbon dots increases signal to noise ration. The PCDs showed thermo-sensing behavior from 0 °C to 90 °C with reasonably good reversibility. The PCDs acted as fluorescent probes for multicolor (green and yellow) imaging of MCF-7 cells while not inducing cell death, which indicates that the PCDs are biocompatible and nontoxic to the cells. Therefore, the PCDs can be used as probes for cell-imaging applications in vitro and in vivo. The PCDs proved to be a multi-purpose polymer carbon nanomaterial that can used for pharmaceutical analysis, bio-imaging and thermo-sensing while providing high accuracy, selectivity and a limit of detection in the nano range.

Nifedipine (NIF), as one of the dihydropyridine calcium channel blockers, is widely used in the treatment of hypertension. However, misuse or ingestion of NIF can result in serious health issues such as myocardial infarction, arrhythmia, stroke, and even death. It is essential to design a reliable and sensitive detection method to monitor NIF. In this work, an innovative molecularly imprinted polymer dual-emission fluorescent sensor (CDs@PDA-MIPs) strategy was successfully designed for sensitive detection of NIF. The fluorescent intensity of the probe decreased with increasing NIF concentration, showing a satisfactory linear relationship within the range 1.0 × 10 -6  M ~ 5.0 × 10 -3  M. The LOD of NIF was 9.38 × 10 -7  M (S/N = 3) in fluorescence detection. The application of the CDs@PDA-MIPs in actual samples such as urine and Qiangli Dingxuan tablets has been verified, with recovery ranging from 97.8 to 102.8% for NIF. Therefore, the fluorescent probe demonstrates great potential as a sensing system for detecting NIF., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

A spectrofluorimetric method using fluorescent carbon dots (CDs) was developed for the selective detection of azelnidipine (AZEL) pharmaceutical in the presence of other drugs. In this study, N-doped CDs (N-CDs) were synthesized through a single-step hydrothermal process, using citric acid and urea as precursor materials. The prepared N-CDs showed a highly intense blue fluorescence emission at 447 nm, with a photoluminescence quantum yield of ~21.15% and a fluorescence lifetime of 0.47 ns. The N-CDs showed selective fluorescence quenching in the presence of all three antihypertensive drugs, which was used as a successful detection platform for the analysis of AZEL. The photophysical properties, UV-vis light absorbance, fluorescence emission, and lifetime measurements support the interaction between N-CDs and AZEL, leading to fluorescence quenching of N-CDs as a result of ground-state complex formation followed by a static fluorescence quenching phenomenon. The detection platform showed linearity in the range 10-200 μg/ml (R 2  = 0.9837). The developed method was effectively utilized for the quantitative analysis of AZEL in commercially available pharmaceutical tablets, yielding results that closely align with those obtained from the standard method (UV spectroscopy). With a score of 0.76 on the 'Analytical GREEnness (AGREE)' scale, the developed analytical method, incorporating 12 distinct green analytical chemistry components, stands out as an important technique for estimating AZEL., (© 2024 John Wiley & Sons Ltd.)

This study introduces a practical and cost-effective method for tracking diltiazem (DLZ) analytically. It utilizes a fluorimetric approach that relies on the modulation of fluorescence intensity of a dye called erythrosine B. Through a one-pot experiment performed in an acidic environment, a complex is rapidly formed between DLZ and erythrosine B. By observing the decrease in erythrosine B emission, a linear calibration plot is established, enabling the detection and quantification of DLZ concentrations ranging from 40 to 850 ng/ml. The estimated limits of detection and quantitation were 10.5 and 32.1 ng/ml, respectively. The variables affecting the DLZ-dye complex system were carefully adjusted. The validity of the approach was confirmed through a thorough evaluation based on the criteria set by ICH guidelines. The accuracy and precision of the methodology were evaluated, and the standard deviation and relative standard deviation were below 2. The strategy was successfully employed to analyze DLZ in tablets and capsules, and no significant variation between the proposed and reported methods as the values of the estimated t-test and F-test at five determinations were below 2.306 and 6.338, respectively. Notably, the method adheres to the principle of green chemistry by utilizing distilled water as the dispersing medium., (© 2024 John Wiley & Sons Ltd.)

Pharmaceutical development of solid-state formulations requires testing active pharmaceutical ingredients (API) and excipients for uniformity and stability. Solid-state properties such as component distribution and grain size are crucial factors that influence the dissolution profile, which greatly affect drug efficacy and toxicity, and can only be analyzed spatially by chemical imaging (CI) techniques. Current CI techniques such as near infrared microscopy and confocal Raman spectroscopy are capable of high chemical and spatial resolution but cannot achieve the measurement speeds necessary for integration into the pharmaceutical production and quality assurance processes. To fill this gap, we demonstrate fast chemical imaging by epi -detected sparse spectral sampling stimulated Raman scattering to quantify API and excipient degradation and distribution.

A sensitive, selective, precise and stability-indicating high-performance thin-layer chromatographic (HPTLC) method is developed for the simultaneous estimation of remogliflozin etabonate and vildagliptin in the presence of their degradation products. The separation was performed in thin layer chromatography plate precoated with silica gel G60F254. The mobile phase consists of methanol:ethyl acetate:toluene:ammonia (1.5:4:4.5:0.1, v/v/v/v). Detection and quantification are performed with densitometer at 212 nm. The Rf values of remogliflozin etabonate and vildagliptin are 0.53 and 0.42, respectively. Degradation studies for the two drugs were carried out in acidic, alkaline, neutral, oxidative, photolytic and thermal stress conditions and analyzed. The suitability of this method for the quantitative determination of the compounds is proved by validation in accordance with the requirements laid down by International Conference on Harmonization (ICH). Linearity was found over the concentration range of 200-1000 ng/band with correlation coefficient of 0.9936 for remogliflozin etabonate and 100-500 ng/band with correlation coefficient of 0.9912 for vildagliptin. The method was successively applied to tablets containing two drugs and found to have no chromatographic interferences from the tablet excipients. The degradant formed was not interfering with estimation of two drugs makes the method more selective for the purpose intended., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The prokinetic drug, prucalopride (PCP) succinate, was determined using a new spectrofluorimetric approach with a highly sensitive, rapid, and simple procedure. The method exploited the enhancement of the inherent native fluorescence of PCP by micellar aggregation with sodium lauryl sulfate (SLS) as an anionic surfactant. Different factors that could affect the fluorescence intensity were carefully studied in order to achieve the maximal fluorescence signal. Measurement of the enhanced fluorescence was done at 354 nm after the excitation at 276 nm. The fluorescence intensity-concentration plot was rectilinear in the concentration range of 50-600 ng/ml with detection and quantitation limits of 13.9 and 42.1 ng/ml, respectively. The method underwent validation according to the International Council for Harmonisation criteria in order to assess its analytical performance, and promising results were achieved that proved the validity and reliability of the method. Furthermore, the method was employed effectively for the analysis of the cited drug in commercial pharmaceutical tablets., (© 2023 John Wiley & Sons Ltd.)

Hydroxyethylcellulose (HEC) is a non-ionic water-soluble polymer with poor mucoadhesive properties. The mucoadhesive properties of hydroxyethylcellulose can be improved by modifying it through conjugation with molecules containing maleimide groups. Maleimide groups interact with the thiol groups present in cysteine domains in the mucin via Michael addition reaction under physiological conditions to form a strong mucoadhesive bond. This will prolong the residence time of a dosage form containing this modified polymer and drug on mucosal surfaces. In this study HEC was modified by reaction with 4-bromophenyl maleimide in varying molar ratios and the successful synthesis was confirmed using 1 H NMR and FTIR spectroscopies. The safety of the newly synthesised polymer derivatives was assessed with in vivo planaria assays and in vitro MTT assay utilising Caco-2 cell line. The synthesized maleimide-functionalised HEC solutions were sprayed onto blank tablets to develop a model dosage form. The physical properties and mucoadhesive behavior of these tablets were evaluated using a tensile test with sheep buccal mucosa. The maleimide-functionalised HEC exhibited superior mucoadhesive properties compared to unmodified HEC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Food and Drug Administration (FDA) recently approved co-formulated celecoxib and tramadol for the treatment of acute pain in adults. Three spectrophotometric methods were efficiently applied to estimate the co-formulated Celecoxib and Tramadol in their tablets; second derivative 2D-spectrophotometry technique (method I), induced dual-wavelength technique (method II) and dual-wavelength resolution technique (method III). The proposed methods were successfully validated following the International Council for Harmonisation (ICH) guidelines and statistically assessed based on the correlation coefficients, relative standard deviations as well as detection and quantitation limits. The obtained results revealed non-significant differences compared to the reported results as revealed by the variance ratio F test and Student t test. Moreover, the applied techniques were further assessed concerning their greenness based on the analytical eco-scale method revealing an excellent green scale with a final score of 95. The proposed spectrophotometric techniques could be applied for the routine analysis and quality control of the studied drugs in their dosage form., (© 2023. The Author(s).)

Background: Before it spreads to other tissues, mebendazole (MBZ), a highly effective broad-spectrum anthelmintic, is used to treat worm infestations caused by roundworms, hookworms, whipworms, threadworms (pinworms), and the gastrointestinal form of trichinosis., Objective: The development of new methods for sensitive quantification of MBZ in the presence of its degraded product is the main objective of the presented research., Method: Validated chromatographic techniques with high sensitivity (HPTLC and UHPLC) are used. The HPTLC method was adopted on silica gel HPTLC F254 plates using ethanol, ethyl acetate, and formic acid (3: 8: 0.05, by volume) as a developing system. Furthermore, the UHPLC method is a green isocratic method with a mobile phase containing methanol and 0.1% sodium lauryl sulphate (20:80, v/v)., Results: The suggested chromatographic methods are greener than the reported ones in terms of the used greenness assessment methods. To validate the developed methods, International Council on Harmonization (ICH/Q2) guidelines were followed. Successful application of the proposed methods was revealed by the simultaneous analysis of MBZ and its major degradation product, 2-amino-5-benzoylbenzimidazole (ABB). The linear ranges were 0.2-3.0, 0.1-2.0 µg/band for the HPTLC method and 2.0-50, 1.0-40 µg/mL for the UHPLC method for MEB and ABB, respectively., Conclusions: The suggested methods were used to analyze the studied drug in its commercial tablets. Both pharmacokinetic studies and quality control laboratories can make use of the suggested techniques., Highlights: Green and accurate HPTLC and UHPLC methods for the determination of MBZ and its major degradation products., (© The Author(s) 2023. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Marbofloxacin (MAR) is an antimicrobial belonging to the fluoroquinolone class and is marketed in the form of tablets. There is no microbiological monograph in official compendia to evaluate the potency of the final product. Furthermore, the literature is scarce in this context., Objective: The objective is to develop and validate a microbiological method by turbidimetry to evaluate the potency of MAR-based tablets, based on the principles of green analytical chemistry., Methods: Purified water-ethanol (9 + 1, v/v) was used as diluent to prepare the MAR solutions at concentrations of 0.25, 0.8, and 2.56 µg/mL, brain heart infusion (BHI) broth as culture media, E. coli American Type Culture Collection (ATCC) 25922 at 10% and incubation in a shaker at 37°C for 4 h were used in the method., Results: The method was: linear in the range of 0.25 to 2.56 µg/mL; selective against the sample adjuvants; precise (intra-day RSD 2.26%, inter-day RSD 3.49%, and inter-analyst RSD 3.59%); accurate with a recovery of 100.20%; and robust against changes in culture medium volume in the tube, shaker rotation, and incubation temperature in the shaker. The potency of MAR tablets was 96.98% using the proposed method., Conclusion: The turbidimetric method developed is a new, fast, and optimized option to the routine QC of MAR in tablets, since it allows the evaluation of the drug's potency in the final product and can be used to complement the results of the physicochemical analysis, in addition to being a green and sustainable alternative., Highlights: The work shows an ecological and green alternative to the routine microbiological pharmaceutical analysis of MAR tablets., (© The Author(s) 2022. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Tinidazole (TIN) has amoebicidal, giardicidal, antifungal, and antimicrobial activities. It is marketed in the form of tablets. Analytical methods to assess the quality of TIN-based products are essential for correct pharmacotherapy., Objective: The objective of this review is to show an overview of the existing analytical methods for evaluating TIN, according to the quality control (QC) analysis routine and green analytical chemistry (GAC)., Results: Official compendia show a method for evaluating TIN in tablets by nonaqueous titration, which has limitations (materials on the mg scale using solvents considered not recommended and harmful). The literature shows some analytical methods for evaluating TIN, both physicochemical and microbiological. The most used physicochemical method is UV (41%), and second is HPLC (28%). Among the microbiological methods, agar diffusion and turbidimetric methods are equally divided. The most studied matrix is TIN tablets (73%), and the most used solvent is methanol., Conclusions: The literature shows space for the development of analytical methods according to GAC for evaluating TIN, optimizing time, resources, and materials, reducing waste generation, and opting for less aggressive reagents, solvents, and diluents., Highlights: This review shows the status of analytical methods, both physicochemical and microbiological, for the analysis of TIN in pharmaceutical matrix, in the context of routine analysis of the chemical-pharmaceutical industries and of GAC., (© The Author(s) 2022. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Newly, baricitinib (Olumiant) is FDA-confirmed for treating adult patients with slightly to highly active rheumatoid arthritis who have a terrible reaction to several treatments against the tumor necrosis factor. The efficacy and safety of baricitinib have been determined by the FDA, so, a precise, and sensitive stability-indicating RP-HPLC method is issued to determine baricitinib and its degradation products in their film-coated tablet dosage form; application to content uniformity and in-vitro dissolution studies., Methods: The analysis of assay and dissolution tests are released using an isocratic elution system while impurities are performed using gradient profile for mobile phase comprising of Buffer Solution: Methanol in Proportion (65:35, v/v) at flow rate 1.0mL/minute, column BDS Hypersil C18 5μm 150×4.6mm, column temperature 30̊C, injection volume 10μL, detection wavelength 290nm using DAD detector., Results: Calibration charts are acquired in the linearity range (1-30μg/mL) of baricitinib with a correlation coefficient=0.9999 with good recovery results between (99-100%)., Conclusion: The proposed procedure was fully validated regarding Linearity, Accuracy, LOD, LOQ, Precision, Robustness, and Specificity, and there is no overlapping owing to deterioration peaks. Furthermore, the method has been accomplished to study content uniformity testing and in-vitro dissolution., (Copyright © 2022 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

Background: Ascorbic acid (ASC; vitamin C) is a weak chromophore, so its presence cannot be determined directly by spectrophotometry., Objective: This work aims to develop and validate a simple and ecofriendly analytical method for the determination of ASC concentration based on the reaction of ASC with the metal complex, ferric salicylate., Methods: The visible absorbance of ferric salicylate was found to be inversely proportional to the concentration of ASC. The possible mechanism of the reaction between ASC and ferric salicylate was investigated: ferric salicylate was found to be reduced by ASC under the applied experimental conditions. Different parameters that may affect the reaction were also investigated: ferric salicylate concentration, pH, ionic strength, and the time of reaction. The optimum concentration of ferric salicylate was found to be 1000 µM and the optimum pH was 5.5. The developed method was validated according to International Conference on Harmonization (ICH) guidelines., Results: The linearity range of the developed method was 5-70 µg/mL and the correlation coefficient was 0.9994. The limits of detection and quantitation were 0.38 µg/mL and 1.16 µg/mL, respectively. The method was successfully applied to the determination of ASC concentration in commercial Ruta-C60® tablets. The mean recovery ± standard deviation was found to be 101.10 ± 0.70%. The results were statistically compared to those obtained by a reported HPLC method. Good agreement was observed., Conclusion: The developed method is simple, fast, cost-effective, and suitable for routine pharmaceutical analysis of ASC., Highlights: The developed method is more sensitive than the other spectrophotometric methods reported for determination of ASC., (© The Author(s) 2022. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Near-infrared (NIR) spectroscopy is a non-destructive, efficient and convenient detection technology, with the emergence of portable NIR spectrometers, NIR mobile applications (APPs) come into being. The popularity of intelligent mobile phones provides an impetus to the research and development of NIR APPs, however, the primary functions such as operating the NIR spectrometers and collecting data cannot satisfy NIR users in the field of data processing. Herein, we propose an APP processing NIR data locally at the mobile terminal, by the comprehensive utilization of Principal Component Analysis (PCA) and Cuckoo Search algorithm optimized Support Vector Classifier with radial basis function (RBFSVC) kernel (CS-RBFSVC). 738 NIR samples of four drugs (Cydiodine Buccal Tablets, Sulfasalazine Enteric-coated Tablets, Dexamethasone Acetate Tablets, Vecuronium Bromide for Injection) were used as the validation objects to train and test the data classification model. Firstly, the original data were subjected to dimensional reduction through PCA for the purpose of compressing calculation amount. Secondly, the CS-RBFSVC model was utilized to classify the types of drugs and their manufacturers, moreover, the improved accuracy and efficiency by introducing Cuckoo Search (CS) algorithm into RBFSVC were proven in comparison with the conventional grid optimized RBFSVC (Grid-RBFSVC) and Linear Support Vector Classifier (Linear-SVC). Last but not least, an APP based on the proposed PCA and CS-RBFSVC model is developed and demonstrated to be able to classify the type of drugs with an accuracy of 100%, the accuracies of classifying the drugs' manufacturers were 100%, 100%, 98.3% and 90.7%, respectively. Conclusively, the proposed PCA and CS-RBFSVC based model can provide a low-consumption, high accuracy and quick strategy for NIR data classification and overcome the limitations of internal storage and operating speed at phone terminals, in conjunction with the portable NIR spectrometer, it is believed to push forward NIR technology into the instant detection and on-site inspection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

A sensitive, specific and eco-friendly reversed-phase-HPLC method was developed and validated for the determination of paracetamol, caffeine and drotaverine HCl along with their related impurities. The separation was accomplished using an X-bridge C 18 column (5 μm; 250 mm × 4.6 mm inner diameter) and a green mobile phase consisting of methanol and 0.02 M phosphate buffer at pH 5.0 in the gradient elution mode. The detector used was a diode array detector. The proposed method was validated in accordance with the International Conference on Harmonisation guidelines. Linear regressions were found in the range of 1-100, 1-100, 2-60, 1-20, 0.50-30 and 1-15 μg/mL for paracetamol, caffeine, drotaverine HCl, p-aminophenol, theophylline and 3,4-dimethoxyphenylacetic acid, respectively. The suggested method was successfully applied for the determination of the studied drugs in their tablet dosage form without interference from any excipients. No discernible difference was found between the obtained results and official or reported methods, statistically, in terms of both accuracy and precision. Dissolution profiling of the studied tablet was also performed using the suggested procedure. Moreover, the greenness profile was assessed using three different tools, namely, the National Environmental Methods Index, the Analytical Eco-Scale and the Analytical GREEnness Metric Approach. The acquired results assert the agreement of the assay with green chemistry principles., (© 2022 John Wiley & Sons Ltd.)

From the seed of Aesculus hippocastanum L., a complex mixture of triterpene saponin glycosides known as aescin was isolated, purified and characterized to be an active pharmaceutical ingredient for preparing of drug products. A reversed phase high performance liquid chromatographic method with UV detection was developed for the determination of total triterpene glycosides in enteric coated tablets containing aescin in a pattern-oriented manner. The mobile phase consisted of a mixture of acetonitrile and 0.1 % phosphoric acid solution (40: 60). UV detection was performed at 220 nm. The chromatographic column was Gemini C18 column, 5 µm 250 mm × 4.6 mm, which was maintained at 25 ◦C, connected with a precolumn (C18, 4.0 × 3.0 mm, 5 µm). The linear range was from 53.4 to 160.1 μg·mL -1 . The RSD of intra-and inter-day precision variations were less than 1 % and the mean recovery was (100.66 ± 0.49) % (RSD = 0.64 %). The method showed its suitability, simplicity, rapidity and precision. Accordingly, it was proven adequate for quality control of this herbal drug product either for registration with the regulartory authority or routine analysis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

A novel electrochemical sensor based on the electro-deposition of silver nanoparticles (AgNPs) on Tropaeolin OO (poly-TO) layers over pencil graphite electrode (PGE) surface was fabricated for the first time for voltammetric determination of flibanserin (FBS); a drug enhances female sexual performance. Further characterization studies using cyclic voltammetry (CV), square wave voltammetry (SWV), electrochemical impedance spectroscopy (EIS) and scanning electron microscopy (SEM) were conducted. The AgNPs synergistic effect on poly-TO layers facilitates the FBS electro-oxidation in phosphate buffer solution (pH 6.0) and its determination in bulk form, tablets and in human plasma. Following ICH guidelines, validation of the proposed SWV method for FBS analysis was successfully achieved using the fabricated sensor (AgNPs@poly-TO/PGE). Under the optimal instrumental and experimental conditions, the anodic oxidation peak current was directly proportional to FBS concentration in the range from 0.1 to 8.5 μmol L−1 with low detection and quantitation limits (0.0286 and 0.0867 μmol L−1, respectively). High sensitivity, selectivity as well as easiness of fabrication are the main advantages of the modified sensor. [Display omitted] • A novel sensor (AgNPs@poly-TO/PGE) was fabricated for the first time. • The fabricated sensor studied the behavior of Tropaeolin OO dye decorated with AgNPs for voltammetric analysis of flibanserin in tablets and plasma. • The proposed method showed higher sensitivity (LOD= 28.6 × 10−9 M) than many reported methods. • High selectivity and easiness of fabrication of the modified sensor ensure its wide applicability in drug analysis. [ABSTRACT FROM AUTHOR]

Background: The Central Drugs Standard Control Organization approved a bilayered, uncoated, fixed-dosage combination tablet formulation containing pregabalin (75 mg) and etoricoxib (60 mg) in November 2019 to control prolonged back pain with neuropathic components., Objective: This research aims to create an analytical quality by design-assisted reversed phase (RP)-HPLC method for quantifying pregabalin and etoricoxib in tablet formulation., Methods: The best chromatographic conditions were a Phenomenex C8 column (250 × 4.6 mm, 5.6 μm) and a mobile phase of 0.35% orthophosphoric acid -acetonitrile (1 + 1, by volume). A flow rate of 1 mL/min was used with a detection wavelength of 220 nm., Results: The optimized reversed phase HPLC method was successfully validated by the International Conference on Hormonization guideline Q2(R1). Moreover, the percentage assay of pregabalin and etoricoxib tablet formulation was 99.05 and 100.02% w/w, respectively, using the validated RP-HPLC method., Conclusion: The newly developed analytical quality by design-assisted RP-HPLC method has several advantages, including shortened analytical time (2.65 min and 7.45 min pregabalin and etoricoxib, respectively), efficient separation in terms of well-defined peaks, and a simple mobile phase combination., Highlights: The use of analytical quality by design principles and the design of the experiment tool allowed the detection of influential parameters critical for achieving the most favourable chromatographic conditions for accurately quantifying individual drugs using the RP-HPLC method. The compliance of the results with the ICH criteria validated the method. As a result, adopting the analytical quality by design methodology ensured the development of a more robust method that can generate consistent, dependable, and quality data throughout the process while also saving time., (© The Author(s) 2022. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

A novel, simple and sensitive spectrofluorimetric approach for determination of terbutaline sulphate (TER) and its prodrug bambuterol (BAM) in their pure and pharmaceutical dosage forms was developed. The suggested approach depends on enhancing the native fluorescence of either TER or BAM at 315 and 297.2 nm after excitation at 277 and 259 nm, respectively, using sodium dodecyl sulphate (SDS) as a micellar medium. In the presence of 0.7% w/v SDS, ~1.38-fold and 1.18-fold enhancement is achieved in the relative fluorescence intensity (RFI) of TER and BAM, respectively. The fluorescence-concentration curves were rectilinear over the concentration range 0.8-16 μg ml -1 , with detection limits (LOD) of 0.252 and 0.26 (μg ml -1 ), quantitation limits (LOQ) of 0.76 and 0.79 (μg ml -1 ), determination coefficients (r2) of 0.9981, and slopes of 45.92 and 10.44 for TER and BAM, respectively. The suggested approach was validated in accordance with International Council for Harmonisation criteria and was effectively applied in the analysis of the studied drugs in their commercial tablets. The high sensitivity of the proposed approach allows its application in evaluating the content uniformity testing of the studied drugs in their tablets through using the official United States Pharmacopeia criteria. Statistical analogies of the findings with that of the reported methods showed really good harmony and indicated no major differences in precision and accuracy., (© 2022 John Wiley & Sons Ltd.)

A simple and reliable high performance liquid chromatographic (HPLC) method with iodine-azide post-column reaction as a detection system has been developed and validated for determination of methimazole in tablets. A chromatographic separation was achieved on a C18 column with a mobile phase consisting of acetonitrile, water, and 2.5% sodium azide solution (pH 5.5) with isocratic elution (20:30:50, v/v/v). The detection is based on spectrophotometric measurement of the residual iodine (λ = 350 nm) from the post-column iodine-azide reaction induced by methimazole, after mixing an iodine solution containing iodide ions with the column effluent containing azide ions and methimazole. Obtained chromatograms for methimazole showed negative peaks as a result of the decrease in background absorbance. The method developed for methimazole was linear over the concentration range of 0.2-2 µmol L-1. The method is accurate and precise (relative standard deviation, R.S.D. < 4%). The detection limit (defined as S/N = 3) was 0.18 µmol L-1 (3.6 pmol injected amount) for the described compound. The elaborated method was applied to determine methimazole in tablets. [ABSTRACT FROM AUTHOR]

Background: Marbofloxacin (MAR) is an antimicrobial for veterinary use, and it does not have a monograph in an official compendium for the pharmaceutical form in tablets., Objective: In this context, the objective of this work was to develop and validate an effective, eco-friendly, and indicative of stability method by spectrophotometry in the ultraviolet region (UV) for quantitative evaluation of MAR in tablets., Method: Purified water-ethanol (80:20, v/v) as a diluent, quartz cubette and 296 nm were used., Results: The method was linear in the range of 3-9 µg/mL (0.9994) with detection and quantification limits of 0.39 and 1.18 µg/mL, respectively, selective in the comparison of standard and sample, precise in intraday (RSD 1.20%), interday (RSD 1.68%), and between analysts (RSD 3.26%) levels, exact with average recovery of 100.39% and robust against small changes in wavelength, diluent concentration, and the use of the ultrasound device. The forced degradation test (sample solutions prepared in 0.1 M HCl, 0.1 M NaOH, and neutral conditions and kept at 60°C during 2 h, and exposure to UV 254 nm lamp at ambient temperature during 2 h) showed that the proposed method is able to assess the susceptibility of MAR., Conclusions: The method can be reliably applied in routine analysis of MAR in tablets as well as being stable, eco-friendly, effective, accessible, and following the principles of green analytical chemistry., Highlights: MAR, an antimicrobial for veterinary use, does not have a monograph in an official compendium for final product evaluation. The use of MAR-based products with inadequate quality can leave residues in foods of animal origin and can also contribute to microbial resistance. So, an ecologically correct and reliable method was developed to evaluate MAR in a final product., (© The Author(s) 2022. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Vibrational spectroscopic chemical imaging is an important tool in the pharmaceutical industry for characterising the spatial distribution of components within final drug products. The applicability of these techniques is currently limited by the long data acquisition times required to obtain high-definition chemical images of a sample surface. Advancements in quantum cascade laser (QCL) technology have provided an exciting new opportunity for infrared (IR) imaging. Instead of collecting a full IR spectrum at each point, it is possible to focus on distinct spectral bands to reduce imaging data collection time. This study explores a laser direct infrared (LDIR) chemical imaging approach that couples QCL technology with rapid scanning optics to provide high-definition chemical images at an order of magnitude faster than traditional imaging techniques. The capabilities of LDIR chemical imaging were evaluated for pharmaceutical formulations and compared with other established spectroscopic chemical imaging techniques including Raman, near-infrared (NIR) and scanning electron microscopy-energy dispersive X-ray (SEM-EDX) spectroscopy with regards to data acquisition time and image quality. The study showed that LDIR imaging provided high-definition component distribution maps comparable to Raman and SEM-EDX at orders of magnitude faster in terms of time. The ability to obtain high-definition chemical images of the whole tablet surface in relatively fast time frames indicates LDIR imaging could be a promising tool in the pharmaceutical industry to rapidly characterise the size and distribution of components within tablets and could help enhance drug product manufacturing understanding.

A new sensitive spectrofluorimetric technique has been established for the estimation of midodrine hydrochloride. This method depends on the condensation reaction of ortho-phthalaldehyde with the primary aliphatic amine of midodrine in the presence of 2-mercapto-ethanol. The pH of the medium was adjusted to 9.0 using 0.1 M borate buffer. The fluorescence of the product was measured at wavelength of 451 nm after excitation at 334 nm. The method was rectilinear over a concentrations range of 0.1 to 1.5 µg mL -1 . The lower detection and quantitation limits were 31 and 94 ng mL -1 , respectively. The method was investigated following the guidelines of the International Council of Harmonization. Analysis of commercial tablet dosage form was carried out successfully by the current method with excellent recovery percentages and with no influence from coexisted pharmaceutical additives .This method was used to evaluate the uniformity of the contents of commercial tablets according to the United States Pharmacopoeia., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The presented quadruple divisor spectrophotometric method was able to resolve and analyze a complex quintuple drug matrix with severe overlapped spectra without previous separation or extraction steps or need of complicated apparatus like chromatographic methods and had the advantage of being green as the solvent used was water., Method: A simple, sensitive, and precise quadruple devisor spectrophotometric method was developed for simultaneous determination of metformin, glipizide, and sitagliptin in the presence of metformin potential impurities melamine and cyanoguanidine. The proposed method was applied for analysis of metformin, glipizide, and sitagliptin in pure form and pharmaceutical formulation (tablets). The developed method was validated and met the requirements for ICH guidelines with respect to linearity, accuracy, precision, specificity, and robustness., Results: A linear response was observed in the range of 2-27, 2-20, 1-20, 0.5-10, and 1-10 μg/mL for metformin, glipizide, sitagliptin, melamine, and cyanoguanidine, respectively, with a correlation coefficient of 0.9996, 0.9998, 0.9997, 0.9997, and 0.9996 for metformin, glipizide, sitagliptin, melamine, and cyanoguanidine, respectively., Conclusions: The validated method was successfully applied for determination of the studied drugs in Janumet® and Engilor® tablets; moreover, the results were statistically compared to those obtained by the reported RP-HPLC method and no significant difference was found between them, indicating the ability of the proposed method to be used for routine quality-control analysis of these drugs., Highlights: Novel application of quadruple divisor spectrophotometric technique is introduced for resolving mixtures containing five components with severely overlapping spectra. A simple and sensitive spectrophotometric method was developed for simultaneous determination of metformin, glipizide, and sitagliptin in the presence of metformin potential impurities melamine and cyanoguanidine. The validity of the proposed method was revealed as per ICH guidelines., (© The Author(s) 2021. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

In this paper, the classical least-squares (CLS) method with molecular absorption spectrophotometric measurement was used to determine simultaneously paracetamol (PAR), ibuprofen (IBU), and caffeine (CAF) in tablets. The absorbance spectra of the standard solutions and samples were measured over a wavelength from 220 to 300 nm with a 0.5 nm step. The concentration of PAR, IBU, and CAF in the sample solutions was calculated by using Visual Basic for Applications (VBA) and a program called CLS-Excel written in Microsoft Excel 2016. The method and the CLS-Excel program were tested on mixed standard laboratory samples with different PAR, IBU, and CAF concentration ratios, and they showed only small errors and a satisfying repeatability. An analytical procedure for tablets containing PAR, IBU, and CAF was developed. The reliability of the procedure was proved via the recovery and repeatability of the analysis results with an actual tablet sample and by comparing the mean contents of active substances in the tablets obtained from the analytical procedure with the HPLC method. The procedure is simple with a reduced cost compared with the HPLC standard method.

We report on the spectral selection of excitation wavelength towards selective detection of aluminum and iron ions using dual emission polymer carbon dots (PCDs). PCDs were prepared from glucose and dilute sulfuric acid using one-pot solvothermal method. The PCDs emit blue light at 480 nm when excited at 340 nm, while emit red light at 590 nm when excited with 400 nm. Spectral selection (selection of excited state) showed sensitivity enhancement for detection of some metal ions. The PCDs showed fluorescence enhancement when combined with Al3+ ions with hypsochromic shift centered at 470 nm when excited at 440 nm. While the PCDs selectively quenched via addition of Fe3+ ions, when excited at 400 nm. The wavelength selection of the same carbon dots increases signal to noise ration. The PCDs showed thermo-sensing behavior from 0 °C to 90 °C with reasonably good reversibility. The PCDs acted as fluorescent probes for multicolor (green and yellow) imaging of MCF-7 cells while not inducing cell death, which indicates that the PCDs are biocompatible and nontoxic to the cells. Therefore, the PCDs can be used as probes for cell-imaging applications in vitro and in vivo. The PCDs proved to be a multi-purpose polymer carbon nanomaterial that can used for pharmaceutical analysis, bio-imaging and thermo-sensing while providing high accuracy, selectivity and a limit of detection in the nano range. [ABSTRACT FROM AUTHOR]

Background: Marbofloxacin (MAR), a second-generation fluoroquinolone, is used in veterinary medicine in the form of tablets. It has a broad spectrum of action, low toxicity, and limited development of bacterial resistance. The analytical methods available in the literature become more important since MAR in tablets does not have a monograph in official compendiums., Objective: Our purpose is to review the methods according to the analyzed matrix and place them according to the conditions used in the scope of green analytical chemistry, in addition to discussing possible gaps and opportunities for the development of new methods., Results: MAR, being an antimicrobial, presents both physicochemical (93%) and microbiological (7%) methods in the literature. Among the methods found, 53% are for analysis of food matrixes using preferably HPLC and TLC-MS, 27% are for analysis of biological matrixes and 20% are for analysis of pharmaceutical matrixes, and in both HPLC is preferably used., Conclusion: Therefore, there is still a gap in the literature in relation to other analytical methods for the analysis of MAR, which are faster, such as microbiological turbidimetry, sustainable, such as miniaturized methods, and ecologically correct, such as those that do not use toxic organic solvents., Highlights: A review of the analytical methods available in the literature for assessing the quality of MAR and MAR-based products in which the methods, as well as new opportunities for analysis according to green analytical chemistry, were described and discussed., (© AOAC INTERNATIONAL 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

As one of the widespread phenols in nature, gallic acid (GA) has attracted a subject of attention due to its extensive biological properties. It is very important and significant to develop a sensitive and selective gallic acid sensor. In recent years, owing to their reversible covalent binding with Lewis bases and polyols, boronic acid compounds have been widely reported as fluorescence sensors for the identification of carbohydrates, ions and hydrogen peroxide, etc. However, boronic acid sensors for specific recognition of gallic acid have not been reported. Herein, a novel water-soluble boronic acid sensor with double recognition sites is reported. When the concentration of gallic acid added was 1.1 × 10 -4  M, the fluorescence intensity of sensor 9b decreased by 80%, followed by pyrogallic acid and dopamine. However, the fluorescence of the sensor 9b combined with other analytes such as ATP, sialic acid, and uridine was basically unchanged, indicating that the sensor 9b had no ability to recognize these analytes. Also, sensor 9b has a fast response time to gallic acid at room temperature, and has a high binding constant (12355.9 ± 156.89 M -1 ) and low LOD (7.30 × 10 -7  M). Moreover, gallic acid content of real samples was also determined, and the results showed that this method has a higher recovery rate. Therefore, sensor 9b can be used as a potential tool for detecting biologically significant gallic acid in actual samples such as food, medicine, and environmental analysis samples., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The objectives of this research were to study the changes of phenolic compounds in vegetable (yellow VS green) tablets with/without probiotics (Lacticaseibacillus rhamnosus LR5) supplementation by using high performance liquid chromatography and probiotic survivability through the simulated gastrointestinal tract. The green vegetable tablets with/without probiotics had a greater (p ≤ 0.05) phenolic content compared to the yellow ones. There were no significant differences of most phenolic compound contents between probiotic-supplemented vegetable tablets and non-probiotic supplemented ones (p > 0.05). The contents of ferulic acid, epicatechin, tannic acid and rutin for both vegetable tablets tended to decrease through passing the stomach (1 and 2 h) and small intestine (2 and 4 h), however, the content of catechin in the yellow vegetable tablets tended to increase. The results also showed that the survival of Lacticaseibacillus rhamnosus LR5 slightly decreased through the simulated gastrointestinal tract. The vibrations from FTIR appeared in the wave length of 4000-3100, 3000-2800 and 1652-1545 cm -1 , which accounted for the change in the N-H bonds of the amine group, changes in the structure of fatty acids and the change of carbonyl groups, respectively. This work highlighted the opportunity of application of probiotics in food products; especially non-dairy foods for consumer with dairy allergy., (© 2022. The Author(s).)

There has been no assessment of the greenness of the described analytical techniques for the simultaneous determination (SMD) of caffeine and paracetamol. As a result, in comparison to the greener normal-phase high-performance thin-layer chromatography (HPTLC) technique, this research was conducted to develop a rapid, sensitive, and greener reversed-phase HPTLC approach for the SMD of caffeine and paracetamol in commercial formulations. The greenness of both techniques was calculated using the AGREE method. For the SMD of caffeine and paracetamol, the greener normal-phase and reversed-phase HPTLC methods were linear in the 50-500 ng/band and 25-800 ng/band ranges, respectively. For the SMD of caffeine and paracetamol, the greener reversed-phase HPTLC approach was more sensitive, accurate, precise, and robust than the greener normal-phase HPTLC technique. For the SMD of caffeine paracetamol in commercial PANEXT and SAFEXT tablets, the greener reversed-phase HPTLC technique was superior to the greener normal-phase HPTLC approach. The AGREE scores for the greener normal-phase and reversed-phase HPTLC approaches were estimated as 0.81 and 0.83, respectively, indicated excellent greenness profiles for both analytical approaches. The greener reversed-phase HPTLC approach is judged superior to the greener normal-phase HPTLC approach based on numerous validation parameters and pharmaceutical assays.

A novel capillary-based fluorescence microsensor for artemisinin was developed with functional polyoxometalates (POMs) as nanozyme by a layer-by-layer self-assembly strategy. Vanadomolybdophosphoric heteropoly acid (H 5 PMo 10 V 2 O 40 , PMoV 2 ) and tungstophosphoric heteropoly acid (Na 5 PW 11 O 39 Cu, PW 11 Cu) with high peroxidase-like activity were synthesized and immobilized on capillary to catalyze artemisinin/thiamine reaction and generate the amplified fluorescence signal. The wide linear range up to 13.0 μM with the low limit of detection of 0.03 μM (S/N = 3) was achieved for the determination of artemisinin by using the proposed POMs-microsensor. The method has been successfully used to detect artemisinin in human plasma and antimalarial drugs with satisfactory accuracy. This work developed a novel capillary fluorescence microsensor with functional POMs as nanozyme, which can serve as a promising candidate in fluorescence microanalysis., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

A versatile surface-enhanced Raman scattering (SERS) assay has been established that can realize rapid and sensitive determination of sildenafil (SIL) and pioglitazone hydrochloride (PIO) adulteration in healthcare products. Metal-organic frameworks-silver nanoparticles (MOFs-AgNPs) with SERS activity were successfully prepared via in situ synthesis AgNPs on the MOFs surface. By virtue of the adsorptivity of MOFs, the MOFs-AgNPs could effectively concentrate the drug molecules on the electromagnetic enhancement areas of AgNPs. Moreover, the MOFs-AgNPs substrate exhibited more sensitive SERS activity than classical AgNPs with linear range of 1.0 × 10 -7 -1.0 × 10 -5  mol L -1 for SIL and 8.0 × 10 -7 -3.0 × 10 -5  mol L -1 for PIO and limit of detection (LOD) of 4.8 × 10 -8  mol L -1 for SIL and 1.4 × 10 -7  mol L -1 for PIO. The designed method realized the determination of SIL and PIO in commercial tablets and healthcare products with recoveries of 93.8-108.0% and 93.0-104.0%, respectively, with relative standard deviation (RSD) of 2.7-4.1% and 2.2-4.2%, respectively. The present system displayed little interference effect on determination. This work provides a multifunctional route for the determination of other drugs via the SERS technology., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)