Innovative UV Protocols Based on Straightforward Mathematical Filtration for Concurrent Estimation of Two Antidiabetic Drugs in Their Brand-New Combination: A Comparative Study.

BACKGROUND: In 2019, the U.S. Food and Drug Administration approved a brand-new combination of linagliptin and empagliflozin in a formulation called Glyxambi® tablets for managing type 2 diabetes mellitus. Nowadays, spectrophotometric techniques occupy the first place among their peers in terms of ease of application, friendliness to the environment, and low costs. OBJECTIVE: This research discusses the development of two very simple spectrophotometric protocols based on zero-order spectra for the determination of linagliptin and empagliflozin. METHODS: The developed protocols were the induced dual-wavelength and absorption correction protocols. Linagliptin could be determined directly at 305 nm, at which the empagliflozin spectrum was zero-crossing. Empagliflozin was determined using the two developed protocols. The induced dual-wavelength technique was developed by calculating the equality factor of linagliptin to cancel its interference. The absorption correction technique was developed by measuring the correction absorption factor. RESULTS: The concentration ranges of linagliptin and empagliflozin were 1-10 µg/mL and 3-30 µg/mL, respectively. Excellent recovery results were found in bulk, dosage form, and synthetic mixtures. Low LOD and LOQ values were obtained, indicating the high sensitivity of the protocols. The statistical Student's t-test was performed to compare the results of the applied and reported protocols, indicating no difference between them. CONCLUSION: The proposed protocols have the advantages of being straightforward, affordable, and requiring no sophisticated manipulations, just simple mathematical calculations. The proposed protocols are acceptable for routine usage in QC laboratories and in future research applications. HIGHLIGHTS: Two novel univariate methods were developed for quantitative analysis of linagliptin and empagliflozin in their pharmaceutical and laboratory mixtures, and produced satisfactory results.

Eco-friendly-assessed micellar-fluorimetric platform for concurrent analysis of empagliflozin and prucalopride succinate in biological fluids: Docking simulation.

Fluorescence spectroscopy has an important role in the determination of very small quantities of substances, especially in biological fluids. For this reason, most analysts have adopted the use of this technique in their biological studies and research, which helps them in the determination of any substance found in trace amounts. In addition to the high sensitivity of the fluorimetric technique, it has the advantages of simplicity and being green for the environment. All these reasons encourage the use of fluorimetric spectroscopy for quantifying co-administered therapy in biological fluids, which is considered a crucial step for patients, particularly in emergent cases requiring monitoring of administered therapeutic drugs. In this work, a sensitive, simple, economic, and environmentally friendly fluorimetric analytical technique was developed for the simultaneous determination of prucalopride succinate (a novel anti-constipation agent) and empagliflozin (an anti-diabetic agent) in pharmaceutical forms and spiked plasma depending on third-derivative signal processing at 333 and 314 nm, respectively. Conventional fluorescence spectra of both drugs showed a large overlap that hindered their simultaneous determination. So, third-order derivative fluorescence was adopted to overcome this overlap. The third-derivative corresponding to each spectrum was recorded using data points = 17 and a scaling factor of 10. The greenness of the proposed method was evaluated using an eco-scale scoring system, revealing excellent greenness. Analytical method parameters were validated following ICH guidelines. The method showed high sensitivity, covering a concentration range of 50-1100 ng/mL and 4-500 ng/mL for empagliflozin and prucalopride, respectively, allowing the pharmacokinetic study of both drugs in biological fluids. The LOD values were 14.09 and 0.91 ng/mL, while the LOQ values were 42.72 and 2.77 ng/mL for empagliflozin and prucalopride, respectively.

Earth-friendly-assessed silver-nanoparticles spectrophotometric method for rapid and sensitive analysis of Molnupiravir, an FDA-approved candidate for COVID-19: application on pharmaceutical formulation and dissolution test.

Molnupiravir is the first oral direct-acting antiviral prodrug recently approved for the COVID-19 pandemic. Here and for the first time, we present a novel, sensitive, robust, and simple silver-nanoparticles spectrophotometric technique for molnupiravir analysis in its capsules and dissolution media. This spectrophotometric technique involved silver-nanoparticles synthesis through a redox reaction between the reducing agent (molnupiravir) and the oxidizing agent (silver nitrate) in presence of polyvinylpyrrolidone as a stabilizing agent. The produced silver-nanoparticles have an intense surface plasmon resonance peak at 416 nm where the measured absorbance values were utilized for the quantitative analysis of molnupiravir. The produced silver-nanoparticles were recognized by using the transmission electron microscope. Under optimal conditions, a good linear rapport was accomplished between molnupiravir concentrations and the corresponding absorbance values in a range of (100-2000) ng/mL with a detection limit of 30 ng/mL. Greenness assessment was implemented using eco-scale scoring and GAPI disclosing the excellent greenness of the suggested technique. The suggested silver-nanoparticles technique was authenticated according to recommendations of the ICH and statistically assessed with the reported liquid chromatographic method without significant differences regarding accuracy or precision. Accordingly, the suggested technique is deemed a green and cheap alternative for assaying molnupiravir due to its reliance primarily on water. Furthermore, the suggested technique's high sensitivity can be employed for investigating molnupiravir bioequivalence in future studies.

Comparative study of four innovative earth-friendly platforms for rapid analysis of daclatasvir dihydrochloride: Application on different matrices.

BACKGROUND: Daclatasvir dihydrochloride has important roles not only in the management of COVID-19 pandemic symptoms but also in the treatment of chronic hepatitis C infection. OBJECTIVE: The current research presents four novel and simple platforms including silver-nanoparticles spectrophotometric technique and three electrochemical conductometric ones for daclatasvir analysis in its tablet, biological fluids, and dissolution media. METHODS: The spectrophotometric platform involved the synthesis of silvernanoparticles through a redox reaction between the reducing agent (daclatasvir) and the oxidizing agent (silver nitrate) in presence of polyvinylpyrrolidone as a stabilizing agent. The produced silver-nanoparticles have an intense surface plasmon resonance peak at 421 nm where the measured absorbance values were utilized for quantitative spectrophotometric determination of daclatasvir. While the electrochemical conductometric platforms involved the reaction of daclatasvir with three different precipitating reagents (silver nitrate, phosphomolybdic acid, and ammonium reineckate) to form ion associates between these reagents and daclatasvir in the aqueous system. RESULTS: All proposed platforms were validated in line with recommendations of the international conference on harmonization producing satisfactory outcomes within the agreed boundaries. CONCLUSION: The proposed platforms are green alternatives for routine rapid assay of daclatasvir at the cheapest cost because their results were observed to be nearly similar to those of the reported platform. Moreover, the suggested spectrophotometric platform's sensitivity can be employed for investigating daclatasvir bioequivalence.

Micellar-enhanced and green-assessed first-derivative synchronous spectrofluorimetric approach for concurrent determination of alfuzosin hydrochloride and solifenacin succinate in different matrices: Docking simulation.

Alfuzosin hydrochloride (AZH) is co-formulated with solifenacin succinate (SOS) in Solitral® capsules for treating prostate hyperplasia in patients with overactive bladder syndrome. Herein and for the first time, an ultrasensitive synchronous spectrofluorimetric approach coupled with first-order derivative signal processing was designed for simultaneous determination of AZH and SOS in their pure forms, newly-released pharmaceutical capsules, and human biological fluids. AZH and SOS showed their conventional emission spectra in bi-distilled water at 382 nm and 294 nm after excitation at 325 nm and 250 nm, respectively. The native fluorescence intensities of AZH and SOS were greatly enhanced through micellar formation using sodium dodecyl sulfate surfactant (2%). The proposed approach included the use of synchronous mode at Δλ of 60 nm where the overlap between the studied analytes' fluorescence spectra wasn't completely resolved. The complete resolution was achieved by derivatization of the synchronized spectra to the first-order yielding two zero-crossing points which allowed the determination of AZH and SOS simultaneously without interference at 408 nm and 321 nm, respectively. Under optimum experimental circumstances, good linearities were accomplished over the concentration ranges of (1-24) ng/mL and (4-250) ng/mL with LOD of 0.26 ng/mL and 1.31 ng/mL for AZH and SOS, respectively. The proposed approach was validated successfully according to guidelines adopted by the ICH and compared statistically with the reported LC method with no discernible differences concerning accuracy or precision at p = 0.05. Successful application of the proposed approach achieved with excellent recovery percentages for analysis of the studied analytes in different matrices (pharmaceutical capsules and biological fluids) confirms its suitability for use in QC laboratories and other bioanalytical applications. The proposed approach's greenness was evaluated using two tools namely; penalty points scoring system and green analytical procedure index (GAPI) divulging excellent greenness of this approach relative to the reported LC method. The proposed approach relied chiefly on water as the cheapest and greenest solvent.

Role of multiparametric magnetic resonance imaging in the diagnosis and staging of urinary bladder cancer.

Objectives: To assess the role of multiparametric magnetic resonance imaging (mp-MRI) in the diagnosis and staging of urinary bladder cancer (BC). Materials and methods: Fifty patients diagnosed with bladder masses underwent mp-MRI study. The results of 3 image sets were analyzed and compared with the histopathological results as a reference standard: T2-weighted image (T2WI) plus dynamic contrast-enhanced (DCE), T2WI plus diffusion-weighted images (DWI), and mp-MRI, including T2WI plus DWI and DCE. The diagnostic accuracy of mp-MRI was evaluated using receiver operating characteristic curve analysis. Results: The accuracy of T2WI plus DCE for detecting muscle invasion of BC was 79.5% with a fair agreement with histopathological examination (κ = 0.59); this percentage increased up to 88.6% using T2WI plus DWI, with good agreement with histopathological examination (κ = 0.74), whereas mp-MRI had the highest overall accuracy (95.4%) and excellent agreement with histopathological data (κ = 0.83). Multiparametric MRI can differentiate between low- and high-grade bladder tumors with a high sensitivity and specificity of 93.3% and 98.3%, respectively. Conclusions: Multiparametric MRI is an acceptable method for the preoperative detection and accurate staging of BC, with reasonable accuracy in differentiating between low- and high-grade BC.

Innovative Earth-Friendly UV-Spectrophotometric Technique for In Vitro Dissolution Testing of Miconazole Nitrate and Nystatin in Their Vaginal Suppositories: Greenness Assessment.

BACKGROUND: The combined mixture of miconazole nitrate (MIC) and nystatin (NYS) has proven its efficiency as a prodigious remedy to cure women's frequent infections: vaginal mycosis and vaginal candidiasis. OBJECTIVE: A novel green spectrophotometric technique, namely the Fourier self-deconvolution method (FSD), was employed for the quantitative determination of MIC and NYS in their pure and pharmaceutical forms without prior separation. Moreover, the proposed technique was first employed to study the dissolution profile of the cited drugs in their pharmaceutical formulation according to FDA recommendations without excipient interference. METHOD: The FSD method is based on a simple mathematical manipulation of zero-order spectra of the cited drugs, which suffered from severe overlapping, so zero-order spectra of the cited drugs were deconvoluted using the Fourier wavelet function in spectrophotometer software. The deconvoluted amplitudes for MIC and NYS were measured at 255 nm and 320 nm, respectively. RESULTS: Linearity ranges were 70-700 µg/mL for MIC and 1-25 µg/mL for NYS. The greenness of the proposed technique was assessed using two assessment tools, namely eco-scale scoring and green analytical procedure index (GAPI), revealing the excellent greenness of this technique. The proposed technique was validated consistent with ICH guidelines and statistically compared to the reported method with no significant differences between them. CONCLUSIONS: The proposed technique has advantages of being simple, time-saving, and noting need any modification to be suitable for quantitative analysis of MIC and NYS in both pharmaceutical and laboratory mixtures. HIGHLIGHTS: An innovative FSD method was developed for quantitative analysis of MIC and NYS in their synthetic and pharmaceutical mixtures and applied for in vitro dissolution testing of their pharmaceutical mixture, producing satisfactory results.

Utility of Silver-nanoparticles for Nano-fluorimetric Determination of Vancomycin Hydrochloride in Pharmaceutical Formulation and Biological Fluids: Greenness Assessment.

Vancomycin hydrochloride (VANH) is a glycopeptide antibiotic commonly employed in the prophylaxis and therapy of various gram-positive bacterial life-threatening infections. Due to the narrow therapeutic window of VANH, its serum levels should be well-monitored to avoid its toxicity and to optimize its therapy. Herein, an innovative silver-nanoparticles enhanced fluorescence technique was designed for VANH rapid analysis in its pharmaceutical formulation and biological fluids. This technique is based on reinforcement of VANH fluorescence intensity with silver-nanoparticles that were synthesized by a redox reaction between VANH and silver nitrate in NaOH alkaline medium using polyvinylpyrrolidone as a stabilizer. The produced silver-nanoparticles were characterized by using UV-visible spectroscopy where they have an intense absorption maximum at 415 nm and transmission electron microscope (TEM) micrograph where they are spherical in shape with smooth surface morphology and size of 10.74 ± 2.44 nm. The fluorescence intensity was measured at 394 nm after excitation at 259 nm. Under optimum conditions, a good linear relationship was accomplished between the VANH concentration and the fluorescence intensity in a range of (1-36) ng/mL with a limit of detection of 0.29 ng/mL. Greenness assessment was performed using two assessment tools namely; eco-scale scoring and green analytical procedure index revealing excellent greenness of the proposed technique. The proposed technique was validated according to the International Conference on Harmonisation (ICH) recommendations and statistically compared with the reported HPLC method revealing no significant difference concerning accuracy and precision at p = 0.05. The proposed technique depended primarily on water as a cheap and eco-friendly solvent.

Smart UV-spectrophotometric platforms for rapid green analysis of miconazole nitrate and nystatin in their combined suppositories and in vitro dissolution testing.

Miconazole nitrate (MIC) and nystatin (NYS) combination has proven its effectiveness as a prodigious therapy to cure women's common infections; vaginal candidiasis and vaginal mycosis. Herein, six smart UV-spectrophotometric platforms depending on minimal mathematical manipulation steps were first introduced for the simultaneous green analysis of MIC and NYS in their pure forms and commercial vaginal suppositories without any preliminary separation steps. These platforms included dual-wavelength, ratio difference, mean centering of ratio spectra, first derivative ratio, ratio subtraction, and absorption correction methods. All of the aforementioned platforms could estimate MIC in a linear range of 90-900 µg/ml. While NYS was computed directly by zero-order spectrophotometry at its λmax (304 nm) in a linear range of 1-15 µg/ml without any interference by MIC even in low or high concentrations. Dual-wavelength and zero-order spectrophotometric platforms were successfully applied to study the dissolution profile of MIC and NYS in their combined formulation in compliance with FDA recommendations without excipients interference. According to ICH guidelines, all platforms were validated regarding the accuracy, precision, and selectivity producing satisfactory results within the accepted limits. Also, the suggested platforms' results were statistically compared with each other and with those of the reported HPLC platform revealing no significant difference concerning accuracy and precision at p = .05. Accordingly, all proposed platforms are regarded as economic and eco-friendly alternatives to the expensive chromatographic platforms that utilize hazardous organic solvents during the analysis of cited drugs.

Comparative study of novel green UV-spectrophotometric platforms for simultaneous rapid analysis of flumethasone pivalate and clioquinol in their combined formulation.

Flumethasone pivalate (FP) and clioquinol (CL) formulation was developed as a prodigious remedy to cure the external ear inflammatory disorders. So, the current research introduces five smart and novel UV-spectrophotometric platforms relying on minimal mathematical manipulation steps for simultaneous green analysis of FP and CL with no preliminary separation in their formulation that suffered from the high difference of their ratio and severe spectral overlapping. These platforms involved dual-wavelength, first derivative ratio, Fourier self-deconvolution, area under the curve, and bivariate methods. The suggested platform' linearity was observed over the concentration range of 3-42 µg/ml for FP and 1.5-8 µg/ml for CL. All suggested platforms were validated according to ICH recommendations regarding accuracy, precision, repeatability, and selectivity producing satisfactory results within the accepted limits. These platforms were represented as rapid, green, and cheap alternatives to the reported chromatographic method due to lower solvent consumption and waste generation. Furthermore, they improved the determination sensitivity of the studied drugs and enhanced the recorded data signals or its spectral resolution by the newly introduced Fourier self-deconvoluted method. The statistical comparison between the results of the suggested platforms with each other and with those of the reported method showed no significant differences between them.

Cross-cultural adaptation and validation of the Arabic version of the Western Ontario Shoulder Instability Index (WOSI-Arabic).

BACKGROUND: One of the self-assessment tools used in shoulder instability to evaluate patient's quality of life is the Western Ontario Shoulder Instability (WOSI) Index. It is a valid and reliable disease-specific tool that has been translated into many languages. The aim of this study is to cross-culturally adapt the Western Ontario Shoulder Instability (WOSI) Index into Arabic and assess its psychometric properties in patients diagnosed with shoulder instability in order to help surgeons and physical therapists assess patients following an intervention. PATIENTS AND METHODS: Forty-four patients with shoulder instability participated in the study. For validity and reliability, the WOSI, Disability of Arm, Shoulder and Hand questionnaire (DASH) and the American Shoulder and Elbow Surgeons (ASES) questionnaire were completed at baseline and the WOSI again within 1 week. For responsiveness the WOSI was completed 1 week postoperative and again 6 months following the completion of a rehabilitation program. RESULTS: Cronbach's alpha (Internal Consistency) of the WOSI was 0.91 and the intraclass correlation coefficient (ICC) was 0.96 indicating high reliability. The standard error of measurement was 90.2 with the scale 0-2100 and the minimal detectable change was 250 out of 2100 (11.9%). For construct validity, there was a moderate significant correlation between the Arabic WOSI, the DASH and the ASES with r=0.60 and 0.62 respectively. The WOSI was highly responsive with an effect size of 3.17 and a standardized response mean of 2.94. CONCLUSION: The Arabic version of the WOSI is a valid, reliable and responsive tool that can be used to assess patients with shoulder instability. LEVEL OF EVIDENCE: I, Validity and reliability study.