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Simple, sensitive, selective and precise stability-indicating thin-layer chromatographic (TLC) and high-peRformance liquid chromatographic (HPLC) methods were developed for the determination of Buflomedil (BFM) in presence of its acid induced degradation products. Complete degradation was carried out by refluxing 50 mg of pure BFM with 50 mL 5 N HCl for 4 hours and produce two main degradation products (1, 3, 5 Trimethoxybenzene and butane- pyrrolidinium salt). Methods were validated as per the International Conference on Harmonization guidelines ICH Q2A and Q2B. The TLC method employs aluminum TLC plates precoated with silica gel 60F254 as the stationary phase and butanol: ammonia: triethylamine (8:0.5:0.5, v/v/v) as the mobile phase to give compact spots for Buflomedil (Rf= 0.55) and its degradation product (Rf =0.05), the chromatogram was scanned at 272 nm. The HPLC method utilizes a C18 column (Zorbax, 150 mm × 4.6 mm, 5 µm) and a mobile phase consisting of methanol: water: acetonitrile: triethylamine (50:30:20:0.4, v/v/v/v, pH 6.5) at a flow rate of 0.7 mL min-1 for the separation of Buflomedil (RT=3.76) and its degradation product (RT=2.117). Quantitation was achieved with UV detection at 272 nm. The methods were validated in terms of accuracy, precision, linearity, limits of detection, and limits of quantification. Buflomedil was exposed to acid hydrolysis and analyzed by the proposed methods in presence of its degradation products. As the methods could effectively separate the drugs from their degradation products, these techniques can be employed as stability-indicating methods that have been successively applied to pharmaceutical formulations without inteRference from the excipients. [ABSTRACT FROM AUTHOR]

Validated spectrophotometric and chemometric methods were developed tbr determination of Naphazoline Hydrochloride (NAP), Chlorpheniramine maleate (CLO) and Methylene blue (MB) in their ternary mixture. Method A was a spectrophotometric method, where NAP and MB were determined using second derivative (D²) spectrophoto metric method using the peak amplitudes at 299 nm and 337 nm for NAP and MB respectively, while CLO was determined using second derivative ratio (DD²) spectrophotometric method using the peak amplitude at 276.6 nm. Method B used the chemometric techniques; principal component regression (PCR) and partial least squares (PLS) for determination of NAP, CLO and MB using the information contained in the absorption spectra of their ternary mixture solutions. The proposed methods have been successfully applied for the analysis of NAP, CLO and MB in their pharmaceutical formulation and the obtained results were statistically compared with the reported methods. [ABSTRACT FROM AUTHOR]

In the present work, different spectrophotometric methods and one spectrofluorimetric method have been developed and validated for the determination of mosapride citrate in the presence of its acid-induced degradation products. The drug was subjected to stress stability study including acid, alkali, oxidative, photolytic, and thermal stress degradation. The developed spectrophotometric methods included the use of first order derivative (1D), derivative of ratio spectra (1DD), mean centring of ratio spectra (MC) and H-point standard additions (HPSAM) spectrophotometric methods. For 1D method, the peaks amplitudes at 282.8 and 319.6 nm were measured, while for 1DD method those at 308 nm and 323 nm were measured. Mean centring of ratio spectra method used the values at 317 nm for calibration, while for HPSAM the absorbance at 273 and 288.6 nm were used. These methods were successfully applied for determination of mosapride in the concentration range of 5-70 µg.ml−1. The spectrofluorimetric method was based on measuring the native fluorescence of mosapride in 0.1 M NaOH using λexcitation 276 nm and λemission 344 nm and 684 nm with linearity ranges of 50-3000 ng.ml−1 and 50-9000 ng.ml−1, respectively. All the developed methods were validated according to the International Conference on Harmonization (ICH) guidelines and were applied for bulk powder and dosage form. The results obtained were statistically compared to each other using one-way ANOVA testing. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Two specific, sensitive, and precise stability indicating chromatographic methods have been developed, optimized, and validated for Hydrochlorothiazide (HCT) and Spironolactone (SPR) determination in their mixtures and in presence of their impurities and degradation products. The first method was based on thin layer chromatographic (TLC) combined with densitometric determination of the separated spots. The separation was achieved using silica gel 60 F254TLC plates and ethyl acetate–chloroform–formic acid–triethyl amine (7:3:0.1:0.1, by volume) as a developing system. Good correlations were obtained between the integrated peak area of the studied drugs and their corresponding concentrations in different ranges. The second method was based on the high-performance liquid chromatography with ultraviolet detection, by which the proposed components were separated on a reversed phase C18analytical column using gradient elution system with deionized water–acetonitrile (97:3, v/v) for 8 min. Then acetonitrile was successively increased to 35% in the next 2 min, and kept constant in the following 10 min, finally 3% acetonitrile was regained again to stabilize the chromatographic system. The flow rate was maintained at 2 mL/min and the detection wavelength was at 230 nm. Linear regressions were obtained in the range of 4.0–50 μg/mL and 5.0–50 μg/mL for both HCT and SPR, respectively. Different parameters affecting the suggested methods were optimized for maximum separation of the cited components. System suitability parameters of the two developed methods were also tested. The suggested methods were validated in compliance with the ICH guidelines and were successfully applied for determination of HCT and SPR in their commercial tablets. Both methods were also statistically compared to each other and to the reported method with no significant difference in performance. [ABSTRACT FROM AUTHOR]

[Display omitted] • Distribution Maps. • Variables Strength Coefficient VSC. • Raman-CI Microscope. • SIMCA. The ability to detect degradation products of active pharmaceutical ingredients (API) is an essential performance not only for conducting proper stability studies and subsequently gain regulatory approvals; but as well for detecting degradation products during the manufacturing process (In Process Control). Thus, this study aims to present the ability of using Raman Chemical Imaging (Raman-CI) microscope, with its optimum precision, in combination with appropriate chemometrics algorithms, to detect the spectrally similar Salicylic Acid (SA) in Acetylsalicylic Acid (ASA) powder mixture, and then create a chemical distribution map that reflects the distribution of ASA's main degradation product. The generated Hyperspectral images were processed where, a supervised chemometrics soft classifier, Soft Independent Modeling of Class Analogy (SIMCA), is applied to classify pixels and construct the subsequent distribution maps. In addition, due to the challenge of the high structural and spectral similarity between both substances, this study presents a new variable selection and dimensionality reduction technique, called Variable Strength Coefficient (VSC) to maximize the spectral differences and enhance the model precision and selectivity. A High-performance liquid chromatographic (HPLC) method was applied as a reference separation method to assess the results obtained by the proposed technique. The proposed technique was validated, where the obtained results confirmed that Raman Chemical Imaging Microscope, when coupled with SIMCA and VSC, is a powerful tool with outstanding accuracy. In addition, this approach could be suitable in applications where constructing accurate distribution maps of spectrally similar API's is required. [ABSTRACT FROM AUTHOR]

Currently, all researchers are concentrating their efforts on countering the COVID-19 pandemic. The majority of patients are managed at home, according to recent statistics. An OTC triple action combination comprising paracetamol (PAR), aspirin (ASP), and diphenhydramine (DIPH) is commonly given for pain relief, fever control, and as a night-time sleep aid. This combination is currently recommended for COVID-19 patients as part of symptomatic treatment and management. In this work, three smart, simple, accurate, eco-friendly, and cost-effective spectrophotometric methods are developed for simultaneous determination of PAR, ASP, and DIPH in their combined over-the-counter caplet dosage form without any prior separation steps. The first method is the first derivative spectrophotometry (D1) which determined PAR at 259.7 nm. The second one is the dual-wavelength in ratio spectra (DWRS) for determination of ASP at 214.1 and 220.1 nm after using 10.0 μg/mL of PAR as a divisor, where PAR was a constant, and the wavelengths difference equal to zero for DIPH. The third method is the double divisor-ratio difference spectrophotometric one (DD-RD) which was based on using the sum of 15.0 µg/mL of each of PAR and ASP as a double divisor, and the difference in amplitudes was measured at two wavelengths ∆P(214.5–226.0) for determination of DIPH. The developed methods have been validated as per ICH guidelines. Furthermore, the three suggested methods were employed successfully to assay marketed pharmaceutical formulation and to investigate the content uniformity of the dosage units in accordance with the United States Pharmacopeia's guidelines. Finally, the greenness profile of the proposed methods was assessed and compared with the reported method using the analytical eco-scale system, national environmental method index (NEMI), green analytical procedure index (GAPI), and analytical greenness (AGREE) metric. The results from the proposed methods statistically agreed with those obtained by the reported one, with no significant differences in accuracy and precision. [ABSTRACT FROM AUTHOR]

• No reported spectrophotometric method for determination of this quaternary mixture. • The proposed univariate methods utilize simple mathematical calculation. • Multivariate methods surpass univariate methods in solving severe overlap spectra. • Multivariate models have the advantage of being stability indicating methods. Rosuvastatin calcium and fenofibrate are recently co-formulated for treatment of hyperlipidemia. Two selective spectrophotometric approaches were developed, the first is univariate manipulation of spectrophotometric data, where isoabsorptive point and dual wavelength method were applied. The total concentration of rosuvastatin calcium and fenofibrate could be determined at λ = 253.2 nm while rosuvastatin calcium was determined with dual wavelength (λ = 243.5 and 307.9 nm) where linearity was achieved in the range of 2.00–22.00 µg/mL and mean accuracy 100.29 ± 0.568 then, by difference, Fenofibrate was determined in the range of 2.00–22.00 µg/mL and mean accuracy 100.23 ± 0.578. The second approach is a stability indicating multivariate modeling namely principal component regression and partial least squares, where the two drugs were determined in the presence of their degradation products. 17 samples were prepared according to five levels four factors calibration design. The developed models were described by 4 latent variables, and good prediction was evidenced by low root mean square error of prediction. The proposed methods were found to be rapid and simple and required no preliminary separation. Rosuvastatin calcium and fenofibrate were analyzed with mean recoveries 99.54 ± 0.903, 99.88 ± 0.548 and 99.50 ± 0.712, 99.30 ± 0.802, respectively. The two drugs were successfully determined in tablets by the developed methods and the results were compared to HPLC methods, where they were found to be statistically non-significant. [ABSTRACT FROM AUTHOR]

• Evaluation of the greenness profile of three chromatographic methods for determination of brompheniramine, phenylephrine and dextromethorphan. • The use of NEMI, GAPI and Eco-scale methods for the evaluation of the greenesss of the proposed analytical methods. • Analysis of the components of Dimetapp® syrup. The effect of analytical procedures on the environment is a major concern nowadays. Scientists are trying to contribute to eco-friendly practices to reduce the negative impact of chemicals and solvents on the environment and analysts working on the field. This work demonstrates three chromatographic methods for the determination of a cold medication composed of dextromethorphan (DEX), phenylephrine (PHN) and brompheniramine (BRM) in their dosage form. Thin layer chromatography (TLC) was attempted using methanol: methylene chloride: water: acetic acid (7:1:1.5:0.5, v/v/v/v) as a mobile phase and detection carried out at 254 nm. The drugs were separated with good resolution at retention factors 0.54, 0.66 and 0.78 for BRM, DEX and PHN, respectively. Two high performance liquid chromatographic (HPLC) methods were also applied; method A utilized a mobile phase made up of acetonitrile, phosphate buffer and methanol (gradient elution) and green solvents were applied in method B namely; ethanol: water (15:85, v/v). Peaks were detected at 270 nm and the retention times for method A were 2.02, 7.59 and 8.43 min and for method B were 2.04, 4.25 and 4.91 min for PHN, BRM and DEX, respectively. Greenness profiles using three approaches; national environmental method index (NEMI), analytical ecoscale and green analytical procedure index (GAPI) were used to evaluate and compare the developed methods. Finally, statistical analysis was applied and no significant difference regarding accuracy and precision was noted. [ABSTRACT FROM AUTHOR]

Comtrex® tablets composed of paracetamol, pseudoephedrine and brompheniramine are widely used for relieving symptoms related to common cold. This study has overcome the challenging dosage form ratio (250:15:1) and proposed chromatographic methods for analyzing the ternary combination were utilized displaying different apparatus, solvents and sensitivity ranges. Three chromatographic methods namely thin layer chromatography (TLC), high performance liquid chromatography with ultra-violet detection (HPLC–UV) and ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) were developed and validated for the simultaneous determination of the three drugs. Concerning the TLC method, aluminum TLC plates pre-coated with silica gel 60F254 were used and methanol:water:ammonia (9:1:0.1, v/v/v) was applied as a mobile phase; scanning of the plates was carried out at 254 nm. For the HPLC–UV method C18 column was used with an isocratic elution mobile phase composed of water:acetonitrile (75:25, v/v; pH 3.2) and the detection was at 210 nm. For the UPLC-MS/MS method; separation was performed on a UPLC-BEH C18 column with methanol: 0.1% ammonium formate (60:40, v/v) as the mobile phase utilizing diphenhydramine as an internal standard and mass spectrometry was used for detection. The methods were simple, sensitive, accurate and precise. Statistical analysis revealed no significant difference from the reported methods in regard to accuracy and precision. [ABSTRACT FROM AUTHOR]

Paracetamol (PAR), Pseudoephedrine hydrochloride (PSE) and cetirizine dihydrochloride (CET) is a ternary mixture that composes tablets which are popular for the relief of flu in Egypt. The spectra of the drugs were overlapped and no spectrophotometric methods were reported to resolve the mixture. This research proposes four spectrophotometric methods that are efficient and require water only as a solvent. The first method was ratio subtraction-ratio difference method (RSDM) where PAR was initially removed from the mixture by ratio subtraction and determined at 292.4 nm, then PSE and CET were quantified by subtracting the amplitudes of their ratio spectra between 257.0 and 230.0 nm for PSE and between 228.0 and 257.0 nm for CET. The second method was derivative ratio spectra—zero crossing (DRZC) which was based on determining both PSE and CET from the zero-crossing points of the first and third derivative of their ratio spectra at 252.0 and 237.0 nm, respectively while PAR was determined using its first derivative at 292.4 nm. Moreover, the ternary mixture was resolved using successive derivative ratio (SDR) method where PAR, PSE and CET were determined at 310.2, 257.0 and 242.4 nm, respectively. The fourth proposed method was pure component contribution algorithm (PCCA) which was applied to quantify the drugs at their λmax. Recovery percentages for RSDM were 100.7 ± 1.890, 99.69 ± 0.8400 and 99.38 ± 1.550; DRZC were 101.8 ± 0.8600, 99.04 ± 1.200 and 98.95 ± 1.300; SDR were 101.9 ± 1.060, 99.59 ± 1.010 and 100.2 ± 0.6300; PCCA were 101.6 ± 1.240, 99.10 ± 0.5400 and 100.4 ± 1.800 for PAR, PSE and BRM; respectively. The suggested methods were effectively applied to analyze laboratory prepared mixtures and their combined dosage form. [ABSTRACT FROM AUTHOR]

[Display omitted] • A triple-action cramp relief over-the-counter pharmaceutical formulation of paracetamol, caffeine and pyrilamine maleate. • Novel eco-friendly HPTLC-densitometry and HPLC-UV methods for mixture analysis and purity assessment. • Successful applicability in assaying and quality control of the market tablets. • Dissolution profiling of Midol® Complete caplets as an in-vivo efficiency indicator. • Affirming methods sustainability via implementing various greenness and whiteness assessment tools. Over the years, several single-pill combinations have been produced and utilized as an alternative option for treatment of the signs and symptoms of Primary dysmenorrhea. The presence of multiple drugs together poses a challenge for analysts regarding analysis, making it a significant hurdle to overcome. A combination of paracetamol (PAR), caffeine (CAF), and pyrilamine maleate (PYR) is commonly recommended as an over-the-counter triple-action treatment to alleviate mild to moderate premenstrual syndrome symptoms. This study presented two liquid chromatographic methods that simultaneously determine PAR, CAF, and PYR in Midol® Complete caplets along with three officially recognized impurities, namely, p-aminophenol, theophylline, and p-anisaldehyde. The initial approach employed high-performance thin-layer chromatography alongside a densitometric scanning technique. The experimental setup utilized silica gel HPTLC plates as the stationary phase, and ethyl acetate: aqueous ammonium hydroxide (10.0:0.1, v/v) mixture as the developing system. The densitometric scanning was conducted at a wavelength of 210.0 nm. The second approach, developing high-performance liquid chromatographic method coupled with ultraviolet detection. Inertsil ODS-3 C 18 column (250 × 4.6 mm, 5 μm) was used to separate the six compounds effectively. For the experimental procedure, an isocratic elution method was chosen with a mobile phase consisting of a mixture of 0.02 M potassium dihydrogen phosphate buffer acidified with o -phosphoric acid (pH 3.0), and methanol (80:20, v/v) at a flow rate of 1.0 mL/min. UV detection was carried out at a wavelength of 210.0 nm. The two proposed methods have been validated in accordance with ICH recommendations. In addition, the suggested HPLC-UV technique was used to track the release profile of the cited drugs during the in-vitro study. The developed methods were assessed and compared for their environmental impact using various greenness evaluation tools. Additionally, the recently introduced RGB12 model was used to study the whiteness features of the suggested methods. The proposed methods yielded desirable outcomes and are sustainable, simple, affordable, and low-cost, which highly recommends their use in quality control labs. [ABSTRACT FROM AUTHOR]

• Tetracycline HCl, metronidazole and bismuth subcitrate have been combined recently. • An analytical approach for simultaneous determination of these drugs in plasma. • A molecularly imprinted solid-phase extraction with HPLC was employed. • Atomic absorption spectrometry for bismuth subcitrate quantification. • Determination with two related official impurities. The integration of molecular imprinting technique with chromatographic one has a great impact on the assay's selectivity and sensitivity. Herein, a molecularly imprinted solid-phase extraction associated with high performance liquid chromatography (MISPE-HPLC) was employed for simultaneous determination of the co-formulated drugs; tetracycline hydrochloride (TET) and metronidazole (MET), in plasma and in their anti-H-pylori drug for the first time. Two sorts of molecularly imprinted polymers (MIPs) were fabricated using TET and MET as the template molecules, while ethylene glycol dimethacrylate and methacrylic acid were used as a cross-linker and a monomer, respectively. The synthesized MIPs were identified using different techniques. The adsorption–desorption capability of each template was investigated towards its corresponding MIP. The extraction conditions of MISPE was optimized with respect to TET/MIP and MET/MIP sorbent. Bismuth subcitrate (BSC), the third co-formulated drug was analyzed in spiked human plasma using an atomic absorption spectrometric (AAS) method. The performance of the developed methods was assured as per ICH guidelines for analyzing the studied drugs in their pharmaceutical dosage form along with two of their official impurities. In addition, bioanalytical method validation was conducted where linearity was achieved at 2.0–40.0 μg mL−1, 2.0–40.0 μg mL−1 and 5.0–80.0 μg mL−1 for TET, MET and BSC, respectively. [ABSTRACT FROM AUTHOR]

Abstract The electrochemical oxidation of Ezogabine (EZG) based on Graphene Oxide Nanosheets (GO) and Ionic Liquids (IL)-modified carbon paste electrodes (CPE) has been studied using different techniques. GO and IL have a synergetic effect giving rise to highly improved electrochemical responses and provide an advantageous platform for the basis of an electrochemical sensor with excellent performance. Screening for the best experimental conditions was performed by fractional factorial design, while optimization studies were performed with the aid of central composite design. The optimum conditions were located by the use of Derringer's desirability function. The sensing of EZG via square wave voltammetry (SWV) is found to exhibit two wide linear dynamic ranges of 9.89 × 10−7–1.92 × 10−5 M and 1.92 × 10−5–2.0 × 10−4 M at pH 2.0. The limits of detection and quantification were calculated to be 9.86 × 10−8 and 3.28 × 10−7 M, respectively. The suggested sensor has been used successfully for EZG determination in human plasma as real samples. Satisfactory recoveries of analyte from these samples are demonstrated indicating that the suggested sensor is highly suitable for clinical analysis, quality control and a routine determination of EZG. Highlights • First electrochemical method for the determination of ezogabine. • An electrochemical method was developed for the determination of ezogabine at trace levels. • Graphene oxide combined with ionic liquids to improve the detection power of the method. • Real sample analysis without pre-treatment step. • The linear range is found to exhibit two wide linear dynamic ranges with LOD of 9.86 x10-8 M. [ABSTRACT FROM AUTHOR]

An anti-H-pylori co-formulated mixture of tetracycline HCl (TET), metronidazole (MET), and bismuth subcitrate (BSC) is recently available. Only two chromatographic and spectrophotometric methods are reported for determining those drugs simultaneously where the effect of impurities that could be present as well as the biological fluids matrix influence do not be taken into consideration. There is a need to develop an easy-to-use potentiometric technique for analysis of TET, MET, and BSC in their co-formulated capsules, in presence of some official impurities and in spiked human plasma. Three carbon paste electrodes (CPEs) were fabricated for this purpose. Being a solid contact ion-selective electrode, CPE suffers from the creation of a water layer affecting its stability and reproducibility. Besides, it has a common problem in differentiation between two drugs carrying the same charge (positively charged TET and MET). Water layer formation was prevented through inserting polyaniline nanoparticles (≈10.0 nm diameter) between solid contact and ion-sensing membrane in the three proposed sensors. TET and MET interference was overcome by synthesizing a corresponding molecular imprinted polymer (MIP) for each drug. The synthesized MIPs were inserted in equivalent sensing membranes and characterized using several techniques. The suggested MIPs have a noticeable enhanced sensitivity in potentiometric determination. The obtained LODs were 5.88 × 10−8, 5.19 × 10−7, and 1.73 × 10−6 M for TET, MET and BSC proposed CPEs, respectively, with corresponding slopes of 57.37, 56.20, and −57.40 mV decade−1. The proposed potentiometric method makes the detection of the three cited drugs simple, fast, and feasible. This approach is the first for determining three drugs potentiometrically in one combined formulation. The obtained results were compared favorably with previously reported potentiometric methods. [Display omitted] • First potentiometric approach for determination of three drugs together. • Tetracycline, metronidazole and bismuth subcitrate were the model drugs. • Polyaniline nanoparticles were inserted to prevent water layer formation. • Molecular imprinting technology for tetracycline and metronidazole was adopted. • Application in their combined capsule and human plasma. [ABSTRACT FROM AUTHOR]

Favipiravir (FAV) has been approved as an antiviral drug used in pandemic corona virus to treat covid-19. It has an amide moiety susceptible to hydrolysis and degradation in acid medium. Therefore, four simple, sensitive, and accurate stability indicating spectrophotometric methods have been developed for the determination of FAV in presence of its acid induced degradation product. The first method describes direct determination of FAV at 323 nm. Dual wavelength method was the second developed one for FAV quantitation by recording the absorbance difference at 322.7 and 270 nm. The third method involves using first derivative peak to peak amplitude at 338.0 and 308.0 nm, while difference spectrophotometry was the fourth suggested method, and it was based on recording the spectral changes at 361.3 nm as pH changes. The obtained calibration curves were linear over 4.0–22.0 µg/mL. Accuracy of the suggested procedures ranged from 99.11 to100.06, while precision results were from 0.80 to1.68. The developed methods were used to determine FAV in pure powdered form, laboratory-prepared mixtures with their degradation product, and pharmaceutical formulation without interference from its acidic degradation product.The greenness was assessed based on GAPI and ACREE metric and was found to be compatible and in reconciliation with green analytical chemistry concepts. [ABSTRACT FROM AUTHOR]

Background: Analysis of complex mixture containing three or more components represented a challenge for analysts. New smart spectrophotometric methods have been recently evolved with no limitation. A study of different novel and smart spectrophotometric techniques for resolution of severely overlapping spectra were presented in this work utilizing isosbestic points present in different absorption spectra, normalized spectra as a divisor and dual wavelengths. A quaternary mixture of drotaverine (DRO), caffeine (CAF), paracetamol (PCT) and para-aminophenol (PAP) was taken as an example for application of the proposed techniques without any separation steps. The adopted techniques adopted of successive and progressive steps manipulating zero /or ratio /or derivative spectra. The proposed techniques includes eight novel and simple methods namely direct spectrophotometry after applying derivative transformation (DT) via multiplying by a decoding spectrum, spectrum subtraction (SS), advanced absorbance subtraction (AAS), advanced amplitude modulation (AAM), simultaneous derivative ratio ( S1DD), advanced ratio difference (ARD), induced ratio difference (IRD) and finally double divisor-ratio difference-dual wavelength (DD-RDDW) methods. Results: The proposed methods were assessed by analyzing synthetic mixtures of the studied drugs. They were also successfully applied to commercial pharmaceutical formulations without interference from other dosage form additives. The methods were validated according to the ICH guidelines, accuracy, precision, repeatability, were found to be within the acceptable limits. Conclusion: The proposed procedures are accurate, simple and reproducible and yet economic. They are also sensitive and selective and could be used for routine analysis of complex most of the binary, ternary and quaternary mixtures and even more complex mixtures. [ABSTRACT FROM AUTHOR]

Four simple, accurate, sensitive and precise spectrophotometric methods were developed and validated for simultaneous determination of Troxerutin (TXN) and Carbazochrome (CZM) in their bulk powders, laboratory prepared mixtures and pharmaceutical dosage forms. Method A is first derivative spectrophotometry ( D 1 ) where TXN and CZM were determined at 294 and 483.5 nm, respectively. Method B is first derivative of ratio spectra (DD 1 ) where the peak amplitude at 248 for TXN and 439 nm for CZM were used for their determination. Method C is ratio subtraction (RS); in which TXN was determined at its λ max (352 nm) in the presence of CZM which was determined by D 1 at 483.5 nm. While, method D is mean centering of the ratio spectra (MCR) in which the mean centered values at 300 nm and 340.0 nm were used for the two drugs in a respective order. The two compounds were simultaneously determined in the concentration ranges of 5.00–50.00 μg mL −1 and 0.5–10.0 μg mL −1 for TXN and CZM, respectively. The methods were validated according to the ICH guidelines and the results were statistically compared to the manufacturer’s method. [ABSTRACT FROM AUTHOR]

Simple, accurate, and selective methods have been developed and validated for simultaneous determination of a ternary mixture of Chlorpheniramine maleate (CPM), Pseudoephedrine HCl (PSE) and Ibuprofen (IBF), in tablet dosage form. Four univariate methods manipulating ratio spectra were applied, method A is the double divisor-ratio difference spectrophotometric method (DD-RD). Method B is double divisor-derivative ratio spectrophotometric method (DD-RD). Method C is derivative ratio spectrum-zero crossing method (DRZC), while method D is mean centering of ratio spectra (MCR). Two multivariate methods were also developed and validated, methods E and F are Principal Component Regression (PCR) and Partial Least Squares (PLSs). The proposed methods have the advantage of simultaneous determination of the mentioned drugs without prior separation steps. They were successfully applied to laboratory-prepared mixtures and to commercial pharmaceutical preparation without any interference from additives. The proposed methods were validated according to the ICH guidelines. The obtained results were statistically compared with the official methods where no significant difference was observed regarding both accuracy and precision. [ABSTRACT FROM AUTHOR]

[Display omitted] • Determination and purity assessment of a triple-action over-the-counter pharmaceutical combination. • First HPTLC-densitometry and HPLC-DAD determination of a ternary mixture of PAR, ASP, and DIPH. • PAP, PNP, and SAL determination as official degradation and process-related impurities. • Dissolution testing of the dosage form as a biological efficiency indicator. • Greenness profile assessment via NEMI, Analytical Eco-scale, GAPI, and AGREE tools. • Methods' applicability for sustainable quality control of the studied drugs. Nowadays, all researchers are focused on combating the pandemic COVID-19. According to recent statistics, most patients are managed at home. An over-the-counter (OTC) triple action formula containing paracetamol (PAR), aspirin (ASP), and diphenhydramine (DIPH) is widely prescribed for pain, fever and as night-time sleep aid. For COVID-19 patients, this combination is now suggested as part of symptomatic therapy and prophylaxis. In this work, two simple liquid chromatographic approaches were designed for simultaneous determination of PAR, ASP, and DIPH in Excedrin® PM caplets, beside three specified official toxic impurities, namely, p -aminophenol, p -nitrophenol, and salicylic acid. The first method comprised high-performance thin-layer chromatographic separation coupled with densitometric quantification, on silica gel HPTLC 60 F 254 aluminium sheets as the stationary phase, ethyl acetate–methanol-aqueous ammonium hydroxide (10.0: 2.0: 0.1, by volume) as the developing system and scanning was performed at 210.0 nm. The second one is a high-performance liquid chromatography coupled with diode array detector. Successful separation of the six components was performed on XTerra C 18 column with isocratic elution of mobile phase 0.1% triethylamine acidified water: methanol (70:30, v/v) adjusted with o -phosphoric acid to pH 3.0 and methanol (90:10, v/v) with flow rate programming and detection at 210.0 nm. Validation of the proposed methods was performed according to ICH guidelines. Both methods were successfully used for quality control of the cited drugs in their marketed formulation. Moreover, the in-vitro release study was monitored using the proposed HPLC-DAD method. The greenness profile of the proposed methods was assessed and comparatively evaluated through various assessment tools, specifically; the analytical eco-scale system, national environmental method index (NEMI), green analytical procedure index (GAPI) and analytical greenness (AGREE) metric. [ABSTRACT FROM AUTHOR]

Cyclizine (CYZ); an antiemetic compound; is widely misused for its euphoric or hallucinatory effects, either by oral or intravenous routes. The concomitant abuse of CYZ among addicted adolescents contributes to neuromuscular disorders that are life-threatening. Consequently, with the company of 1-Methylpiperazine (MPZ) and diphenylmethanol (DPM, Benzhydrol) as pharmacopoeia-reported CYZ impurities, a novel spectrofluorimetric assay for the detection of CYZ, has been established either in human plasma samples or in its parenteral formulation. The native fluorescence of CYZ has been investigated under various conditions. Different parameters affecting relative fluorescence intensity of CYZ including diluting solvent, surfactant, plasma protein solvent, and pH were studied and optimized. The linearity obtained between the fluorescence intensity at emission wavelength 350 nm after excitation at 244 nm and the corresponding CYZ concentrations was in the range 10–1000 ng/mL for measurement of CYZ either in pure form or in human plasma samples, with a appropriate correlation coefficient (r = 0.9999) and 3.10 ng/mL as the limit of detection and 9.41 ng/mL as the limit of quantitation. The suggested procedure was created and validated in accordance with ICH guidelines for quantification of CYZ either in its pure form or its dosage form, and FDA guidelines for the assay of CYZ in human plasma. Finally, in silico study and ADMET predictions were conducted for the studied drug impurities to estimate their pharmacokinetic behaviors. The results showed that both CYZ impurities have higher cellular permeability and maximum tolerated doses, DPM has higher BBB and CNS permeability than MPZ, while MPZ exceeds DPM in total clearance and volume of distribution. [ABSTRACT FROM AUTHOR]

Point of care (POC), also identified as on-site testing, has evolved as a rapid and accurate technique for drug of abuse screening and analysis. The aim of this work is to detect tropicamide (TPC) abuse in biological fluids; we selected rat plasma as example. We developed a disposal miniaturized, portable, green, and budget-friendly POC solid-state electrochemical sensor based on potentiometric transduction. To attain that, an innovative microfabricated electrode modified with conducting polymer poly(3-octylthiophene) (POT) has been placed on sensitized printed circuit board (PCB). A two-stage optimization process was implemented to develop the fabricated electrode. The first stage of the optimization process depends on screening various ionophores in order to enhance the sensor selectivity towards tropicamide. Copper nanoparticles exhibited the highest selectivity towards TPC. The second stage was utilizing a polymer as an ion-to-electron transducer layer between the copper nanoparticles impregnated ion sensing membrane and the microfabricated solid-contact ion-selective electrode. This polymer was added to boost the stability of the potential drift (1.2 mV/h) due to the hydrophobic behavior of the POT, which precludes the formation of an aqueous layer at the Cu electrode/polymeric membrane interface and improve the limit of detection (1.1 × 10−8 M). Nernstian potentiometric response was accomplished for TPC with a slope of 58.46 ± 0.43 mV/decade and E 0 ∼ 189.39 ± 2.12 over the concentration range 1.0 × 10−7 to 1.0 × 10−2 M. The suggested sensor's intrinsic figure of merits include a quick response time (13 ± 2 s) and long life time (45 days). The proposed sensor has been successfully employed in the selective determination of TPC in pharmaceutical formulations, and biological fluids. When the results were compared to those of the official approach, there was no statistically significant difference. The Eco-Scale tool assessed and measured the greenness profile of the established method. [Display omitted] • Development a portable, disposable, and reliable POC solid-state electrochemical sensor based on potentiometric transduction to detect TPC. • Detection of the TPC abuse lets this method accessible for forensic chemistry and toxicology applications. • The proposed copper based sensors offer an eco-friendly technique. • The proposed sensor has been successfully employed in the selective determination of TPC in pharmaceutical formulations, and biological fluids. [ABSTRACT FROM AUTHOR]

• Two novel chromatographic methods developed for determination of the TPC abuse in rat plasma. • This is the first article related to TPC abuse for detecting traces of the studied drug in rat plasma. • Pharmacokinetic behaviors of tropicamide have been studied for the first time. • Greenness assessment of the proposed methods was investigated and evaluated. • These relied on the simulation of the behavior of abusers for further use in toxicological field. Tropicamide (TPC) is an antimuscarinic ophthalmic solution. Recently, it is reported to be used intravenously for recreational purposes. Misuse of the drug may leads to several effects such as slurred speech, unconsciousness, hallucinations, dysphoria, suicidal feelings, convulsions, and tachycardia. Two rapid and sensitive green chromatographic methods were newly established for detection and quantification of TPC abuse in rat plasma. The proposed TLC-densitometric method relied on the separation of TPC and the internal standard paracetamol (PCM) using a developed system of ethyl acetate: ethanol (9:1, v/v) on TLC silica gel 60 F 254 plates and detection was performed at 210.0 nm. Linearity was achieved over a concentration range of 0.20–5.00 µg/band for TPC using 0.50 µg/band of PCM. On the other hand, the developed RP-HPLC method was based on the separation of TPC and sofosbuvir (SOF) as an internal standard using a mobile phase consisting of ethanol and water in the ratio of (45: 55, v/v) on ZORBAX Eclipse Plus® C18 column (250 × 4.6 mm, 5 µm) at a flow rate of 1.8 mL/ min and UV detection at 210.0 nm. Linearity was obtained over the concentration range of 0.10–30.00 µg/mL for TPC using 10.00 µg/mL of sofosbuvir (SOF) as an internal standard. Different evaluation tools assessed and measured the greenness profile of the established methods. On the validation of developed methods FDA recommendation was followed and all the results obtained agreed with acceptance criteria. The suggested methods were successfully used to study the pharmacokinetic parameters of TPC in rat plasma. This is the first article related to TPC abuse for determining the traces of the studied drug in rat plasma. The developed methods can be used for further monitoring of TPC abuse in addicted people plasma. [ABSTRACT FROM AUTHOR]

Apomorphine is a dopamine agonist that is used for the management of Parkinson's disease and has been proven to effectively decrease the off-time duration, where the symptoms recur, in Parkinson's disease patients. This paper describes the design and fabrication of the first potentiometric sensor for the determination of apomorphine in bulk and human plasma samples. The fabrication protocol involves stereolithographic 3D printing, which is a unique tool for the rapid fabrication of low-cost sensors. The solid-contact apomorphine ion-selective electrode combines a carbon-mesh/thermoplastic composite as the ion-to-electron transducer and a 3D printed ion-selective membrane, doped with the ionophore calix[6]arene. The sensor selectively measures apomorphine in the presence of other biologically present cations – sodium, potassium, magnesium, and calcium – as well as the commonly prescribed Parkinson's pharmaceutical, levodopa (L-Dopa). The sensor demonstrated a linear, Nernstian response, with a slope of 58.8 mV/decade over the range of 5.0 mM–9.8 μM, which covers the biologically (and pharmaceutically) relevant ranges, with a limit of detection of 2.51 μM. Moreover, the apomorphine sensor exhibited good stability (minimal drift of just 188 μV/hour over 10 h) and a shelf-life of almost 4 weeks. Experiments performed in the presence of albumin, the main plasma protein to which apomorphine binds, demonstrate that the sensor responds selectively to free-apomorphine (i.e., not bound or complexed forms). The utility of the sensor was confirmed through the successful determination of apomorphine in spiked human plasma samples. [ABSTRACT FROM AUTHOR]

[Display omitted] • The developed methods are simple, accurate, and precise spectrophotometric methods. • Four methods were used simultaneous determination of glimepiride and pioglitazone hydrochloride. • The methods were successfully applied for the determination of glimepiride and pioglitazone hydrochloride in pure powder and dosage form. • The results obtained were compared statistically with the official one. Simple, accurate, and precise four spectrophotometric methods were developed and validated for simultaneous determination of glimepiride and pioglitazone hydrochloride in their pharmaceutical formulation. The first spectrophotometric method was the dual-wavelength which determined glimepiride at 219.0 and 228.0 nm and pioglitazone hydrochloride at 268.0 nm. The second one is the first derivative of ratio spectra (DD1) spectrophotometry in which the peak amplitudes were used at 238.0 nm and 268.0 nm for glimepiride and pioglitazone hydrochloride, respectively. The third method is ratio subtraction in which glimepiride was determined at 228.0 nm in the presence of pioglitazone hydrochloride which was determined by extended ratio subtraction at 268.0 nm. The fourth method was the ratio difference to determine glimepiride and pioglitazone hydrochloride. Beer's law was confirmed in the concentration range 2.50–15.00 µg mL-1, and 10.00–50.00 µg mL-1 for glimepiride and pioglitazone respectively for the four methods. The proposed methods were used to determine both drugs in their pure powdered form with mean percentage recoveries of 99.91 ± 1.117% for glimepiride and 99.76 ± 0.911% for pioglitazone hydrochloride in method (A). In method (B), the mean percentage recoveries were 100.12 ± 0.89% for glimepiride and 100.02 ± 1.06% for pioglitazone hydrochloride. In method (C) glimepiride was 100.01 ± 0.592% and 99.85 ± 0.845% for pioglitazone hydrochloride by extended ratio subtraction. And finally, in method (D) the mean percentage recoveries were 100.66 ± 0.670% for glimepiride and 99.92 ± 0.988% for pioglitazone hydrochloride. The developed methods were successfully applied for the determination of glimepiride and pioglitazone hydrochloride in pure powder and dosage form. The suggested methods were also used to determine both compounds in laboratory-prepared mixtures. The accuracy, precision, and linearity ranges of the developed methods were determined. The results obtained were compared statistically with the official method, and there was no significant difference between the proposed methods and the official method for accuracy and precision. [ABSTRACT FROM AUTHOR]

• Two different chromatographic methods; HPLC and HPTLC were applied. • Analysis of a ternary mixture of ambroxol, guiafenesin and theophyline. • Determination of the mixture was in the presence of guiacol and caffeine as potential impurities and in the presence of methyl paraben as an additive in syrup dosage form. Two high performance chromatographic methods were developed and validated for the simultaneous determination of Ambroxol, Guaifenesin and Theophylline in pharmaceutical dosage forms and in the presence of Guaiacol and Caffeine as the officially stated impurities. These were a reversed phase liquid and a thin layer chromatographic methods. The liquid chromatographic separation was achieved using Inertsil ODS-3 C 18 column (4.6 mm × 250 mm, 5 μm). Gradient elution was performed using a mixture of solvent A (0.05 M ammonium acetate, pH 3, adjusted with glacial acetic acid) and solvent B (methanol), at a flow rate of 1.0 mL/min. The separated peaks were detected at 260.0 nm. The thin layer chromatography was performed using HPTLC 60 F 254 silica gel plates, mobile phase was consisting of ethyl acetate: methanol: acetic acid (10:0.5:1, v/v/v) and detection was performed at 254.0 nm. Validation of the developed methods was achieved according to International Conference on Harmonization (ICH) guidelines. The proposed methods were fast, accurate, precise, and sensitive. Hence, they could be employed for routine quality control of the ternary mixture in capsule and syrup dosage forms. [ABSTRACT FROM AUTHOR]

Spectrophotometric-assisted chemometric techniques are beneficial for resolving spectral overlapping and are considered comparable to traditional chromatographic methods. In this work, different chemometric approaches were applied for simultaneous determination of Bromhexine HCl (BRHX), Guaifenesin (GUA) and Salbutamol sulphate (SALB) in the presence of Guaiacol (GUAIA), without any prior separation. Two-way and three-way techniques were applied. The resolving power of genetic algorithm (GA-PLS), trilinear partial least square (N-PLS) and multivariate curve resolution (MCR-ALS) were investigated. A set of 17 synthetic samples in the concentration range 10.0–30.0 μg/mL of BRHX, GUA and SALB and 6.0–10.0 μg/mL of GUAIA were used in the construction of the calibration models. Commercially available syrup dosage form was successfully analyzed by the developed methods without interference from formulation additives. The developed models were evaluated through calculation of root mean squared error of prediction (RMSEP), the obtained values were 0.263, 0.419 and 0.342 for BRHX, 0.254, 0.318 and 0.503 for GUA and 0.298, 0.268 and 0.302 for SALB using N-PLS, MCR-ALS and GA-PLS, respectively. The resolving power of the developed models was emphasized through comparison with a reported HPLC method, where no significant difference was found regarding both accuracy and precision. Unlabelled Image • Three chemometric methods were developed to resolve the spectral overlap of three coformulated drugs with listed impurity. • Wavelength selection and use of trilinear data greatly enhance the efficiency of multivariate calibration methods. • Genetic Algorithms as a feature selection technique to spectral data for selecting the most informative variables was applied. • Two different trilinear algorithms; N-PLS & MCR-ALS were applied for the purpose of comparison. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) emerges as a notable health concern among the elderly population. Safinamide mesylate (SAF) is a novel and emerging add-on therapy in PD treatment. The stability of innovative drug formulations and the development of appropriate stability-indicating methods are of great importance to modern pharmaceutical analysis. The current work has established novel comprehensive stability-indicating chromatographic approaches, HPTLC coupled with densitometric quantification and HPLC-DAD, for the selective assay of SAF in pharmaceutical formulation along with its synthetic precursor impurity; 4-hydroxy benzaldehyde (4-HBD) in presence of its stress induced degradation products. The stability of SAF was investigated under different stress conditions. It was found that SAF is likely to undergo acid, base hydrolysis, and oxidative degradation. Using mass spectrometry and infrared spectroscopy, the structures of the forced degradation products were confirmed and elucidated. The dissolution behavior of Parkimedine ® Tablets was also monitored in the FDA suitable medium. Multiple assessment tools were used to evaluate the environmental sustainability of the proposed methods and the reported one. The greenness tools included Complex-GAPI and AGREE metrics. In addition, the innovative concepts of "blueness" and "whiteness" evaluation were incorporated through the newly introduced BAGI and RGB12 algorithms, respectively., (© 2024. The Author(s).)

Methyldopa, a synthesized dopamine substitute with phenolic, amine, and carboxylic groups, was used to create a selective molecular imprinted polymer (MIP) for detecting formoterol fumarate dihydrate (FFD), a long-acting beta2-agonist for asthma and COPD. The bio-inspired polymer (MD) was electro-grafted onto a pencil graphite electrode (PGE) using cyclic voltammetry in a phosphate buffer (pH 6.5). An indirect method involving a redox probe (ferrocyanide/ferricyanide) and differential pulse voltammetry measured FFD binding to the MIP's 3D cavities. The sensor showed a linear response range from 1 × 10⁻⁹ M to 2 × 10⁻¹⁰ M, with a detection limit of 1.7 × 10⁻¹¹ M. The polymethyldopa (PMD) and FFD interaction was assessed by UV spectroscopy, and the method was validated per ICH guidelines. Green analytical approaches, including RGB and GAPI, were also implemented. The goal was to use advances in molecularly imprinted polymers to develop a more precise and selective electrochemical sensor for FFD quantification., (© 2024. The Author(s).)

Indacaterol, a β 2 agonist prescribed for long-term management of patients with chronic obstructive pulmonary disease and asthma. In this study the first MISPE cartridges was developed using indacaterol as a template for its selective extraction from rat lung tissues, enabling precise pharmacokinetic evaluation at the drug's site of action. A molecular imprinting polymer was synthesized using indacaterol as a template, methacrylic acid as a functional monomer and ethylene glycol dimethacrylate as a cross-linker with a molar ratio (1: 4: 20). The polymer was characterized by a high binding capacity of 9840 ± 0.86 and high selectivity with an imprinting factor of 4.53 ± 0.12. The synthesized polymer was utilized as a sorbent in solid-phase extraction to purify and extract indacaterol from lung tissue matrix. The optimum molecularly imprinted solid-phase extraction (MISPE) conditions were 20.0 mg of molecular imprinting polymer and non-imprinting polymer, acetonitrile as the loading solvent, acetonitrile: water (20: 80; by volume) as the washing solvent, and methanol: acetic acid (90: 10; by volume) as the eluting solvent. A pharmacokinetic study was performed for indacaterol in rat lungs using the synthesized and optimized MISPE cartridge as a tool for sample purification. These parameters were determined in the lung tissues of rats emphasizing the local exposure of indacaterol to its target organ. The C max and T max were 51.020 ± 2.810 µg mL - 1 and 0.083 ± 0.001 h, respectively. The AUC 0-24 and AUC 0 - inf were 175.920 ± 1.053 and 542.000 ± 5.245 µg h mL - 1 , respectively. The elimination rate constant was 0.014 ± 0.00012 h - 1 and the half-life time was 48.510 ± 0.012 h. This study successfully developed and optimized MISPE cartridges using indacaterol as a template, enabling precise pharmacokinetic evaluation in rat lung tissues. The cartridges demonstrated high binding capacity and selectivity, providing crucial insights into the local exposure of indacaterol at its site of action., (© 2024. The Author(s).)

Indacaterol, is an ultra-long-acting β2 agonist, glycopyrronium is a long-acting muscarinic-antagonist and mometasone is a synthetic corticosteroid. They were used recently in combination for the treatment of severe asthma symptoms and chronic obstructive pulmonary disease. In this work, it was the first time to develop a green and environment friendly ultra-performance liquid chromatographic method using design expert program for the analysis of the three drugs in their combined dosage form. Also, the method was bioanalytically validated for the analysis of the three drugs in spiked human plasma samples. The method was linear in range from 0.50 to 100.0 μg mL-1 for indacaterol and mometasone and from 1.0 to 150.0 μg mL-1 for glycopyrronium. It showed high accuracy where, the % recovery for indacaterol, glycopyrronium and mometasone in plasma were ranged from 94.27 to 97.86%, 96.43 to 98.75% and 96.86 to 98.43%, respectively. Also, it was precise where, the % relative standard deviation for the inter-day precision was ranged from 2.571 to 3.484%, 3.180 to 4.123% and 3.150 to 3.984% and the intra-day precision was ranged from 2.351 to 3.125%, 2.512 to 3.544% and 2.961 to 3.983% for indacaterol, glycopyrronium and mometasone, respectively. The limit of detection and the limit of quantification for indacaterol and mometasone were 0.03 and 0.10 μg mL-1 while for glycopyrronium, they were 0.16 and 0.50 μg mL-1., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Remdesivir and acetyl salicylic acid are often co-administered medications in the treatment of COVID-19, specifically targeting the viral infection and thromboembolism associated with the condition. Hence, it is essential to establish a technique that enables the concurrent quantification of these pharmaceutical compounds in plasma while also keeping environmentally friendly methods. Accordingly, the aim of this work is to simultaneously determine remdesivir and acetyl salicylic acid through a bioanalytical validated synchronous spectrofluorimetric method with applying principles of green chemistry. Since, the two drugs showed severe overlap after excitation at 242.0 nm, 284.0 nm for remdesivir and acetyl salicylic acid, respectively. The overlap was effectively overcome by using synchronous mode with a wavelength difference (Δλ) of 160.0 nm for remdesivir and 100.0 nm for acetyl salicylic acid. Different parameters have been optimized such as Δλ, solvent, pH and surfactant. A linear calibration was obtained over the concentration range 0.01-4.00 µg/mL for remdesivir and 0.01-3.00 µg/mL for acetyl salicylic acid and the method was precise and accurate. The method was successfully used for the investigation of pharmaceutical formulation and the quantification of the maximum plasma concentration (C max ) of the two drugs. The method has been evaluated as an excellent green analytical method based on three greenness assessment tools., (© 2024. The Author(s).)

A novel, highly sensitive and eco-friendly micellar-mediated spectrofluorimetric method was developed and validated for the determination of the novel antiparkinsonian drug safinamide mesylate in the presence of its related precursor impurity, 4-hydroxybenzaldehyde. The proposed approach relies on increasing the inherent fluorescence emission at 296 nm of safinamide, by forming hydrogen bonds between the mentioned drug and sodium dodecyl sulfate in the micellar system using 0.1 N HCl as a solvent, following excitation at 226 nm. A thorough investigation was conducted into the experimental factors affecting spectrofluorimetric behavior of the studied drug. A linearity plot of safinamide over the concentration range of 10.0-1000.0 ng/mL against the relative fluorescence intensities was established. The proposed method demonstrated excellent sensitivity down to the nano-gram level with detection and quantitation limits of 1.91 and 5.79 ng/mL, respectively. The studied drug was effectively determined in Parkimedine ® Tablets. Furthermore, the proposed method allows for ultrasensitive quantification of safinamide in spiked human plasma, with satisfactory percentage recovery (98.97-102.28%). Additionally, the greenness assessment using the advanced green certificate classification approach, the complementary green analytical procedure index (Complex-GAPI), and the analytical GREEness metric approach (AGREE), along with the practicality check using the Blue Applicability Grade Index in addition to the all-inclusive overall whiteness evaluation using the RGB-12 model were carried out. The outcomes demonstrated the effectiveness and whiteness of the proposed technique. Clearly, the suggested approach has the advantages of being simple, requiring no pretreatment steps, and relying solely on direct measuring procedures., (© 2024. The Author(s).)

The study presents a first electrochemical method for the determination of the immunomodulator drug Baricitinib (BARI), crucial in managing COVID-19 patients requiring oxygen support. A unique electrode was developed by modifying graphite carbon nickel nanoparticles (NiNPs) with functionalized multiwalled carbon nanotubes (f.MWCNTs), resulting in nanohybrids tailored for highly sensitive BARI detection. Comparative analysis revealed the superior electrocatalytic performance of the nanohybrid-modified electrode over unmodified counterparts and other modifications, attributed to synergistic interactions between f.MWCNTs and nickel nanoparticles. Under optimized conditions, the sensors exhibited linear detection within a concentration range from 4.00 × 10 -8 to 5.56 × 10 -5 M, with a remarkably low detection limit of 9.65 × 10 -9 M. Notably, the modified electrode displayed minimal interference from common substances and demonstrated high precision in detecting BARI in plasma and medicinal formulations, underscoring its clinical relevance and potential impact on COVID-19 treatment strategies.

Therapeutic drug monitoring is an important clinical testing of the drugs to monitor their concentrations in plasma in order to guarantee their optimal impact, and to avoid any side effects resulting from drug-drug interactions. A green reversed-phase high-performance liquid chromatographic method using a photodiode array detector (RP-HPLC-PDA) was developed for the simultaneous determination of three carbapenem antibiotics (Imipenem, ertapenem, and meropenem) with the co-formulated drug (cilastatin) and contraindicated drugs (probenecid and warfarin) in spiked human plasma. The separation was achieved at 25 °C using a gradient elution of a mixture of mobile phase A: methanol and mobile phase B: phosphate buffer (pH 3.0). The photodiode array detector was adjusted at 220 nm. Bioanalytical method validation was carried out as per the FDA guidelines, and the method showed good linearity ranges for the six drugs that included their Cmax levels along with low limits of quantification. Based on the results, the method was found to be accurate and precise; with high % recovery and good % RSD, respectively. The method was successfully applied to spiked human plasma, signifying a good potential to be implemented in future TDM studies of these drugs when co-administered together., (© 2024. The Author(s).)

Vilanterol is a once-daily dose inhaler prescribed for asthma and chronic obstructive pulmonary disease. This study involved an investigation of vilanterol stability under acidic, basic, oxidative, thermal, and photolytic stress conditions. UPLC method was developed and validated for the analysis of vilanterol with its degradants. The drug was stable under photolytic and thermal stress conditions and degraded under acidic, basic, and oxidative stress conditions. Degradation kinetics was performed for acidic, basic and oxidative stress conditions. Kinetics parameters, K, half-life time (t 1/2 ) and shelf-life time (t 90 ) were assessed, and the degradation followed first order reaction. The method was linear from 0.10 to 100.00 µg mL -1 with accuracy, inter-day and intra-day precision from 99.45 to 100.02%, 0.391-0.694 and 0.041-0.345, respectively. Mass spectrometry was employed to elucidate the structure of the degradants, and the results revealed that certain degradation products were comparable to vilanterol metabolites. The World Anti-Doping Agency has prohibited the presence of vilanterol and its metabolites in athletes' urine except for exercise bronchoconstriction with limited dose. So, quantification of vilanterol in the presence of its degradants was performed in human urine. The results revealed that the method was linear in range of 1.00 to 100.00 µg mL -1 . Samples collection and experimental protocol was performed according to the guidelines of the Research Ethics Committee of the Faculty of Pharmacy, the British University in Egypt with approval No. CH-2305., (© 2024. The Author(s).)

Background: Biologics are essential in cancer treatment because they stimulate the body's natural response to fight cancer, but they are expensive. Biosimilars are more affordable compared to patent biologicals, but it must be verified that they are as effective as their innovators. Characterization of biosimilars and assessment of interchangeability requires many data points for verification., Objective: The proposed study provides a quality assessment of two new bevacizumab (BVZ) biosimilars, produced by Amgen and Biocad, Inc., through the development and greenness assessment of an orthogonal testing protocol and purity indicating assay, including size-exclusion (SE-HPLC), reversed-phase (RP-HPLC), and cation exchange chromatography (CEX-HPLC) in addition to dynamic light scattering (DLS) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)., Methods: SE-HPLC method was performed and validated to screen the BVZ monomer and its aggregates and/or fragments. Peak purity and system suitability parameters were calculated. Results indicate that the orthogonal protocol is a useful tool for assessing monoclonal antibody stability. It is a key criterion for biosimilarity assessment. DLS and SDS-PAGE results were compared to each other to reveal close retention times and banding patterns between BVZ innovator and its biosimilars. These results showed that Avastin® and the investigated biosimilars have the same profile in terms of peak area of related compounds within the acceptance limit and apparent molecular weight, and the SDS-PAGE technique was found to be the most eco-friendly technique among others., Conclusions: The results obtained highlighted the importance of assessing similarities and differences in ensuring the biosimilarity and interchangeability of the studied products., Highlights: BVZ is one of the essential monoclonal antibodies in the treatment of colorectal cancer (CRC). BVZ biosimilars were evaluated by developing an orthogonal testing protocol and a purity-indicating assay. The size-exclusion (SE)-HPLC method was applied and validated to monitor the BVZ monomer and its aggregates. The results demonstrated the importance of assessing the stability and biosimilarity of BVZ., (© 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.)

Two selective stability-indicating procedures were adopted for the quantification of Solifenacin succinate (SOL) along with its acid degradant, in its powder form or in pharmaceutical tablet. Under stress conditions, the acid degradation pathway of SOL was investigated, its official impurity (SOL imp-A) was obtained as the possible acid degradation product, also. A densitometric technique based on the separation of SOL from SOL imp-A employing HPTLC plates prelaminated with silica gel 60 F254 as the stationary phase and a developing solution containing methanol:chloroform:ammonia (8:1:1, v/v/v) and UV scanning of the developed bands at 220 nm. Linear regression analysis data for the calibration plot of SOL showed perfect linear relationships throughout the range of concentration 10-60 μg/band. A reversed phase C18 analytical column (4.6 × 250 mm, 5 μm) was also used to separate the mixture at a flow rate of 1 mL/min, using acetonitrile:0.05 M phosphate buffer (70:30, v/v) as the mobile phase and phosphoric acid to set pH = 3.5. Quantification was obtained at 220 nm using peak area and linear calibration curve across a concentration range of 10-70 μg/mL. The recommended procedures were applied to the existing dosage form, and they generated satisfactory results., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Reduction of environmental pollution sources is the main target of green chemistry; it is applied across the life cycle of a chemical product. Scientists try to switch to eco-friendly practices to diminish the negative impact of chemicals and solvents on the environment. Analytical chemistry is one of the main fields that mounted green chemistry approach. In this work, sensitive and selective green chromatographic methods with UV detection are described for the simultaneous determination of aspirin, rosuvastatin and clopidogrel. The first proposed method is an RP-HPLC one, which was described and successfully validated for the simultaneous separation and determination of the three components on Prontosil Hyperchom C18 (250 × 4.6 mm, 5 μm) column using an isocratic elution. The second method was a TLC spectrodensitometry in which the three components were separated, identified and quantified. The drugs were applied on silica gel plates, and developed using n-heptane: acetone: glacial acetic acid (60:40:0.4, by volume). The three drugs resolved bands were quantified by spectrodensitometric scanning at 240 nm. Both methods were validated according to ICH, statistically compared to the official methods with full greenness investigation to confirm that the proposed methods are viable alternatives for quality assessment of this combination., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

This work is concerned with exploiting the power of chemometrics in the assay and purity determination of naphazoline HCl (NZ) and pheniramine maleate (PN) in their combined eye drops. Partial least squares (PLS) and artificial neural network (ANN) were the chosen models for that purpose where three selected official impurities, namely; NZ impurity B and PN impurities A and B, were successfully determined. The quantitative determinations of studied components were assessed by percentage recoveries, standard errors of prediction as well as root mean square errors of prediction. The developed models were constructed in the ranges of 5.0-13.0 μg mL -1 for NZ, 10.0-60.0 μg mL -1 for PN, 1.0-5.0 μg mL -1 for NZ impurity B and 2.0-14.0 μg mL -1 for two PN impurities. The proposed models could determine NZ and PN with respective detection limits of 0.447 and 1.750 μg mL -1 for PLS, and 0.494 and 2.093 μg mL -1 for ANN. The two established models were compared favorably with official methods where no significant difference observed., (© 2023. The Author(s).)

Recently, green analytical chemistry (GAC) is a key issue towards the idea of sustainability, the analytical community is focused on developing analytical methods that incorporate green chemistry principles to minimize adverse impacts on the environment and humans. Herein, we present 2 sustainable, selective, and validated chromatographic methods. Initially, lidocaine hydrochloride (LDC) and miconazole nitrate (MIC) with two preservatives; methyl paraben (MTP) and saccharin sodium (SAC) were chromatographed via TLC-densitometric method which employed ethyl acetate: methanol: formic acid (9:1:0.1, by volume) as the mobile phase with UV detection at 220.0 nm, good correlation was obtained in the range of 0.3-3.0 µg/band for MIC and LDC. Following that, RP-HPLC was successfully applied for separating quinary mixture of LDC, MIC, MTP, SAC along with LDC impurity; dimethyl aniline (DMA) using C18 column, and a gradient green mobile phase composed of methanol and phosphate buffer (pH 6.0) in different ratios with a flow rate 1.5 mL/min and UV detection at 210.0 nm, linearity ranges from 1.00 to 100.00 µg/mL for MIC, 2.00-100.00 µg/mL for LDC and 1.00--20.00 µg/mL for MTP and DMA. No records to date regarding the determination of the two drugs, besides MTP and DMA. The proposed methods were validated according to the ICH guidelines and applied successfully to the analysis of the compounds. The methods' results were statistically compared to those obtained by applying the reported one, indicating no significant difference regarding both accuracy and precision. The methods' greenness profiles have been assessed and compared with those of the reported method using different assessment tools., (© 2023. The Author(s).)

Three novel, simple and accurate multivariate spectrophotometric assisted mathematical techniques were developed for determination of paracetamol, caffeine, drotaverine HCl and their related impurities. The used multivariate algorithms are principal component regression (PCR), partial least squares (PLS), and synergy intervals partial least squares (siPLS). Linearity of the suggested methods was found to be (1.00-14.60, 1.40-7.00, 1.40-3.80, 1.00-3.00, 1.50-3.50 and 2.50-4.50 µg/mL) for paracetamol, caffeine, drotaverine HCl, and their related impurities; p-aminophenol, theophylline and homoveratric acid, correspondingly. The presented methods were effectively implemented in the determination of the cited compounds in their laboratory prepared mixtures. Commercially available tablet preparation was also analyzed using the applied methods where no impurities were detected and without interference from tablet additives. Moreover, statistical analysis did not reveal any noticeable differences between the obtained results and those acquired from the reported method in terms of accuracy and precision. The developed multivariate algorithms were validated by means of internal and external validation sets. The obtained results showed the siPLS algorithm's superiority to PCR and PLS according to the values of correlation coefficient values (r) and the lowest root mean square error of prediction (RMSEP). The combination of four subintervals [10, 12, 14, and 17] produced the highest efficiency model. Furthermore, these methods may be an applicable substitute to HPLC ones in quality control laboratories during rush of analyses where several samples have to be analyzed in a short time., (© 2023. Springer Nature Switzerland AG.)

Impurity profiling of a pharmaceutical compound is now taking great attention during quality assessment of pharmaceuticals, as presence of small amount of impurities may affect safety and efficacy. In this work, a novel TLC chromatographic method coupled with densitometric detection was established for the simultaneous quantification of naphazoline HCl, pheniramine maleate and three of their official impurities, namely; naphazoline impurity B, pheniramine impurities; A & B. Chromatographic separation was carried out on TLC aluminum silica plates F254, as a stationary phase, using methanol: ethyl acetate: 33.0% ammonia (2.0: 8.0: 1.0, by volume), as a mobile phase. Plates were examined at 260.0 nm and International Council for Harmonisation (ICH) guidelines were followed for method's validation. Important factors, such as; composition of mobile phase and detection wavelengths were optimized. Linearity was achieved over the ranges of 2.0-50.0 µg band -1 for naphazoline, 10.0-110.0 µg band -1 for pheniramine, 0.1-10.0 µg band -1 for naphazoline impurity B and 2.0-50.0 µg band -1 for both pheniramine impurities. The proposed method was assessed in terms of accuracy, precision and robustness where satisfactory results (recovery % ≈ 100% and RSD < 2) were obtained. The method was also applied for the simultaneous determination of naphazoline HCl and pheniramine maleate, in Naphcon-A ® eye drops, with respective recoveries of 101.36% and 100.94%. Method greenness was evaluated and compared to the reported HPLC one via environmental, health and safety tool. The developed method has much potential over the reported one of being simple, selective, economic and time saving for the analysis of the five cited compounds., (© 2022. The Author(s).)

Recent studies have suggested that irisin may act as a potential neurokine. Exercise and L-carnosine supplementation showed neuroprotective effects in Alzheimer's disease (AD)-like conditions. However, the regulation of irisin in the hippocampus of streptozotocin (STZ)-induced memory impairment and its relation to insulin signalling remain to be investigated. This study was designed to compare the effect of swimming exercise and L-carnosine intake on serum, CSF and hippocampal irisin in rats received intracerebroventricular (ICV) injection of STZ. Rats were recruited in swimming paradigm, received oral carnosine (100 mg/kg/day) or vehicle treated. After 5 weeks, rats were sacrificed after neurobehavioural testing. CSF and serum irisin were determined. Hippocampal tissues were used to assess expression of FNDC5/irisin, BDNF and proteins related to insulin signalling, in addition to β-amyloid peptide and phosphorylated tau protein levels. We observed decreased hippocampal, but not CSF or serum, irisin in ICV-STZ-injected rats. Exercise and carnosine intake almost normalized hippocampal FNDC5/irisin expression which was associated with reduced soluble β-amyloid peptide and phosphorylated tau protein, improved BDNF and insulin signalling proteins, with corresponding mitigated cognitive impairments. However, hippocampal FNDC5/irisin was not correlated with serum or CSF irisin levels. Histologically, both interventions ameliorated the hippocampal damage in STZ-injected rats. The current study reveals that carnosine is equivalent to exercise in reversing cognitive decline and Alzheimer's biomarkers. In both interventions, enhancement of hippocampal FNDC5/irisin and insulin signalling may be involved in mediating these neuroprotective effects., (© 2021. University of Navarra.)

Prednisolone acetate (PDN) is a corticosteroid anti-inflammatory liable to degradation under different conditions and used with antibiotics in eye drops. Two selective stability-indicating separation techniques were developed for simultaneous determination of PDN and moxifloxacin HCl (MXF) binary mixture in pure forms, ophthalmic formulation, in the presence of PDN impurities and in the presence of their degradation products. The first method was based on HPTLC separation using silica gel 60 F254 HPTLC plates, and a developing system of toluene: ethyl acetate: methanol: ammonia (5.0: 6: 2.0: 0.05, v/v/v/v) is used with detection at 254 nm. The second method was HPLC using a mobile phase of acetonitrile: methanol: deionized water, pH 2.8 (25.0: 35.0: 40.0, v/v/v), at 254 nm. A kinetic study utilizing the developed HPLC method for PDN degradation under different stress conditions was performed. Furthermore, the method was applied for determination in rabbit aqueous humor. Validation was conducted as per ICH guidelines, and system suitability was ascertained. The calibration curves were constructed in the range 0.10-25.00 and 0.20-50.00 μg band-1, for PDN and MXF by HPTLC, while for HPLC, it was 0.02-50.00 and 0.10-50.00 μg mL-1 for both drugs, in order., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Nanosized adsorbents when used in potentiometric methods of analysis usually show better performance rather than the traditional potentiometric approach; this is attributed to the high specific surface area of the nanomaterial used in addition to the lack of internal diffusion resistance, thus improving their adsorption capacity. In the presented work, a rapid and sensitive potentiometric determination of chlorpheniramine maleate (CPM) and pseudoephedrine hydrochloride (PSE) in pure form, in pharmaceutical preparation, and in biological fluid was developed based on functionalized magnetic nanoparticles (Fe 3 O 4 ). This strategy was compared with the classical potentiometric strategy. Three types of sensors were constructed using phosphotungstic acid (PTA), β- cyclodextrin ( β- CD), and β -cyclodextrin-conjugated Fe 3 O 4 magnetic nanoparticles for the potentiometric determination of each of CPM and PSE. The prepared sensors were characterized in regards to their composition, life duration, working pH range, and response time. The sensors have demonstrated promising selectivity to CPM and PSE in the presence of pharmaceutical formulation excipients, plasma matrix, and a diversity of both organic and inorganic interfering materials. The developed sensors have displayed good responses. Statistical comparison of the achieved results with a reported method has revealed no significant difference regarding both accuracy and precision.

Multivariate calibration models manipulating UV-spectroscopic data of three anti-productive cough drugs namely ambroxol, guaifenesin and theophylline were constructed for the intent of simultaneous determination in presence of their impurities; guaiacol and caffeine. Both interval partial least squares (iPLS) and synergy interval partial least square (siPLS) algorithms were adopted for variables selection to extract useful information and improve the models' performance. The optimal spectral range and their combinations were assigned according to the lowest value of Root Mean Square Error of Prediction (RMSEP), Standard Error of Prediction (SEP) and Correlation Coefficient (R 2 ). The results obtained from full spectrum PLS were compared with those obtained by iPLS and siPLS. The siPLS method exhibited better performance. The combination of four subintervals, 2, 9, 13, and 16, showed the best effect, with RMSEP of 0.1039, 0.3548 and 0.207 μg/mL, for ambroxol, guaifenesin and theophylline, respectively and correlation coefficient of 0.9999, 0.9975 and 0.9994 for ambroxol, guaifenesin and theophylline, respectively. The proposed methods were used for the simultaneous determination of the three drugs in presence of their impurities in bulk powder and in pharmaceutical formulation., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Cerium oxide nanoparticles (CeO 2 NPs) showed promising effects in neurodegenerative diseases including some animal models of Parkinsonism. However, the implication of CeO 2 NPs in 6-hydroxydopamine (6-OHDA) induced Parkinsonism remains to be investigated., Aim: This study was designed to assess whether CeO 2 NPs treatment could alleviate neurobehavioral and neurobiochemical deficits in 6-OHDA induced neurotoxicity in rats., Material and Methods: 50 rats received left intrastriatal (IS) injection of either saline (control, n = 10) or 6-OHDA (n = 40). At the third week post-lesion, motor dysfunction was verified using neurobehavioral tests. Then diseased rats received intraperitoneal injection of 0.1, 0.5 or 1 mg/kg of CeO 2 NPs or vehicle (10 rats each) for 3 weeks. Rats were subjected to behavioral assessments and then sacrificed for biochemical analyses of the striatum. Striatal dopamine levels, oxidative stress markers including total antioxidant capacity (TAC) and malondialdehyde (MDA), and caspase 3 activity as an apoptotic marker were assessed., Results: Different doses of CeO 2 NPs variably improved motor dysfunctions induced by 6-OHDA injection in open field, Rota Rod and stepping tests. In addition, the neurobiochemical derangements were almost reversed by the 0.5 mg/kg dose of CeO 2 NPs, while 0.1 mg/kg dose was not sufficient to alter biochemical measurements in the striatum. Administration of 1 mg/kg of CeO 2 NPs partially ameliorated striatal dopamine and decreased apoptosis without significant effect on oxidative stress., Conclusion: The present study showed a putative therapeutic role of CeO2NPs in the treatment of 6-OHDA-induced Parkinsonian rats, and suggested their antioxidant and antiapoptotic effects as possible mechanisms for elevated striatal dopamine level and improved motor performance., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Wavelets have been adapted for a vast number of signal-processing applications due to the amount of information that can be extracted from a signal. In this work, a comparative study on the efficiency of continuous wavelet transform (CWT) as a signal processing tool in univariate regression and a pre-processing tool in multivariate analysis using partial least square (CWT-PLS) was conducted. These were applied to complex spectral signals of ternary and quaternary mixtures. CWT-PLS method succeeded in the simultaneous determination of a quaternary mixture of drotaverine (DRO), caffeine (CAF), paracetamol (PAR) and p-aminophenol (PAP, the major impurity of paracetamol). While, the univariate CWT failed to simultaneously determine the quaternary mixture components and was able to determine only PAR and PAP, the ternary mixtures of DRO, CAF, and PAR and CAF, PAR, and PAP. During the calculations of CWT, different wavelet families were tested. The univariate CWT method was validated according to the ICH guidelines. While for the development of the CWT-PLS model a calibration set was prepared by means of an orthogonal experimental design and their absorption spectra were recorded and processed by CWT. The CWT-PLS model was constructed by regression between the wavelet coefficients and concentration matrices and validation was performed by both cross validation and external validation sets. Both methods were successfully applied for determination of the studied drugs in pharmaceutical formulations., (Copyright © 2016 Elsevier B.V. All rights reserved.)

In this work, resolution and quantitation of spectral signals are achieved by several univariate and multivariate techniques. The novel pure component contribution algorithm (PCCA) along with mean centering of ratio spectra (MCR) and the factor based partial least squares (PLS) algorithms were developed for simultaneous determination of chlorzoxazone (CXZ), aceclofenac (ACF) and paracetamol (PAR) in their pure form and recently co-formulated tablets. The PCCA method allows the determination of each drug at its λmax. While, the mean centered values at 230, 302 and 253nm, were used for quantification of CXZ, ACF and PAR, respectively, by MCR method. Partial least-squares (PLS) algorithm was applied as a multivariate calibration method. The three methods were successfully applied for determination of CXZ, ACF and PAR in pure form and tablets. Good linear relationships were obtained in the ranges of 2-50, 2-40 and 2-30μgmL(-1) for CXZ, ACF and PAR, in order, by both PCCA and MCR, while the PLS model was built for the three compounds each in the range of 2-10μgmL(-1). The results obtained from the proposed methods were statistically compared with a reported one. PCCA and MCR methods were validated according to ICH guidelines, while PLS method was validated by both cross validation and an independent data set. They are found suitable for the determination of the studied drugs in bulk powder and tablets., (Copyright © 2016 Elsevier B.V. All rights reserved.)