Spectrofluorometric determination of calcium in the human nasal secretions investigating the association with olfactory function.

Ionic microenvironment of the nasal secretions especially calcium ions play essential role in the olfactory transmission. However, there is a critical need to determine the free calcium levels in healthy people's nasal secretions in contrast to those of patients with olfactory impairment. A selective spectrofluorometric method was created to quantify nasal calcium levels utilizing its quenching ability to the fluorescence of the functionalized carbon quantum dots. The surface of carbon quantum dots was functionalized with calcium ionophore A23187 and ion association complex, calcium phosphotungstate, to improve the selectively to quantify calcium ions. The functionalized carbon quantum dots exhibited a concentration-dependent fluorescence quenching upon interaction with calcium ions. Different factors influencing the quenching process were done to provide efficient analytical process. The new method, demonstrated accurate calcium determination over the concentration range of 200-4000 ng/mL. The suggested technique was used to measure the calcium in the nasal secretions of both healthy people and patients with olfactory impairment. The findings revealed significantly higher calcium levels in the patient with olfactory dysfunction (healthy vs. patient; 735 ± 20 ng/mL vs. 2987 ± 37 ng/mL, p < 0.05).

A fluorescence chemo sensor approach for determination of finerenone in pharmaceutical formulation and human plasma: Method development and validation.

Finerenone, a non-steroidal mineralocorticoid receptor antagonist, has gained recent approval for treating cardiovascular and kidney-related conditions. Herein, an innovative fluorescence chemo sensor was developed for the determination of finerenone in the pharmaceutical dosage form and the plasma matrix. The method is basically based on chemical transformation of finerenone into a fluorescent product through sequential reactions. This transformation occurs through a sequence of steps involving the interaction of finerenone with trimethylamine, resulting in the formation of a nucleophilic intermediate that subsequently reacts with bromoacetyl bromide to form fluorescent product, (S)-N-(2-bromoacetyl)-4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide. The formed fluorescent product exhibits defined emission peak at 338 nm when excited at 248 nm. Significant concentration-dependent fluorescence enhancement was obtained enabling precise finerenone determination in the pharmaceutical formulation and plasma matrix. The method was optimized and validated providing sensitive determination over linearity range of 1-200 ng/mL with a lower limit of detection at 0.280 ng/mL. This strategy provides an efficient, economical substitute and straightforward, more sensitive analytical method for finerenone assessment in various matrices, in contrast to the previously published method, high-performance liquid chromatography-tandem mass spectrometry, which is expensive and time-consuming.

Efficient and eco-friendly detection of gabapentin using nitrogen-doped carbon quantum dots: an analytical and green chemistry approach.

This study presents the development of an eco-friendly and highly selective mitrogen-doped carbon quantum dot based sensor (N-CQDs) for the detection of gabapentin - a commonly misused drug. A detailed characterization of N-CQDs spectral features and their interaction with gabapentin is provided. The optimal conditions for sensing, including pH value, buffer volume, N-CQDs concentration, and incubation time, were established. The results showed excellent fluorescence quenching at 475 nm (λex = 380 nm) due to the dynamic quenching mechanism, and the sensor demonstrated excellent linearity in the 0.5-8.0 µg mL-1 concentration range with correlation coefficients of more than 0.999, a limit of detection (LOD) of 0.160 and limit of quantification (LOQ) of 0.480 µg mL-1. The accuracy of the proposed sensor was acceptable with a mean accuracy of 99.91 for gabapentin detection. In addition, precision values were within the acceptable range, with RSD% below 2% indicating good repeatability and reproducibility of the sensor. Selectivity was validated using common excipients and pooled plasma samples. The proposed sensor accurately estimated gabapentin concentration in commercial pharmaceutical formulations and spiked plasma samples, exhibiting excellent comparability with previously published methods. The 'greenness' of the sensing system was evaluated using the Analytical GREEnness calculator, revealing low environmental impact and strong alignment with green chemistry principles with a greenness score of 0.76. Thus, the developed N-CQDs-based sensor offers a promising, eco-friendly, and effective tool for gabapentin detection in various situations, ranging from clinical therapeutics to forensic science.

Reconstruction of Upper Third Defect of the Auricle by Conchal Cartilage Graft and Coverage by Postauricular Flap.

BACKGROUND: The defects of the upper third of the auricle are considered significant reconstructive challenges, as they require frequent operations with a high risk of morbidity at the donor site and result in unacceptable cosmetic abnormalities. OBJECTIVE: Is to perform the reconstruction of a full-thickness auricular defect located in the upper third of the ear using a conchal cartilage graft with postauricular flap coverage, aiming to minimize both donor and recipient morbidity. PATIENTS AND METHODS: The current study included 20 patients with unilateral upper-third auricular defects. The repair involved 2 components: a cartilage graft from the concha to provide structural support and a flap for coverage. Follow-up was conducted for 6 months after the operation. RESULTS: Successful outcomes were achieved in both subjective and doctors' assessments. Regarding subjective outcomes, 85% of the patients reported high satisfaction (P < .001). In terms of doctors' subjective assessment, 90% of the patients had excellent results (P < .001). Mild early and postoperative complications, if encountered, resolved spontaneously. CONCLUSION: The use of a combined conchal cartilage graft and postauricular flap in treating a full-thickness upper third auricular defect is safe and effective, with no major complications. The technique preserves the cosmetic and functional outcomes of the auricle, providing an excellent color match and minimal donor-site morbidity.

Augmented least squares, a powerful chemometric approach for the spectroscopic analysis of the antiretroviral therapy abacavir, lamivudine and dolutegravir in their ternary mixture.

Augmented least squares models such as concentration residual augmented classical least squares (CRACLS) and spectral residual augmented classical least squares (SRACLS) are powerful chemometric approaches that can be applied for spectroscopic analysis of many pharmaceutical compounds. Herein, both CRACLS and SRACL have been employed for UV spectral analysis of three antiretroviral therapy namely abacavir (ACV), lamivudine (LMV) and dolutegravir (DTG) in their ternary mixture. A partial factorial design has been utilized for calibration set construction then both CRACLS and SRACLS models have been optimized regarding the number of iterations and principal components, respectively, using a leave-one-out cross-validation procedure. It was found that a higher number of iterations and principal components were required for modelling the minor component DTG indicating more augmentation procedures to improve the models' accuracy. Validation of the proposed models was performed using external validation set of 13 mixtures and different validation parameters have been evaluated regarding models' predictive abilities. Both models showed excellent performance for analyzing ACV and LMV with relative root mean square error of prediction (RRMSEP) below 2 %. However, higher RRMSEP values around 5 % were observed for the minor component DTG suggesting that these models should be utilized with caution when analyzing minor components in mixtures. Furthermore, the suggested models have been applied for analyzing ACV, LMV and DTG in their pharmaceutical formulation and excellent agreement was observed between the suggested models and the reported chromatographic method posing these models as powerful chemometric approaches for quality control analysis of many pharmaceutical compounds.

Development of fluorescence chemo sensor for selective histamine determination in spiked human plasma samples.

Histamine is crucial for controlling a variety of physiological processes and its dysregulation is linked to various pathological conditions, including allergic disorders, autoimmune diseases and inflammatory conditions. Herein, a novel fluorescence chemo sensor was produced to measure histamine in the pure form and spiked human plasma matrix. The proposed method is based on chemical transformation of histamine into a fluorescent product, N-(2-(1H-imidazol-4-yl) ethyl)-2-bromoacetamide, exhibiting unique fluorescence properties compared to non-fluorescent histamine molecule. This transformation occurs through a sequence of chemical reactions involving the interaction of histamine with trimethylamine, resulting in the formation of a nucleophilic intermediate that subsequently reacts with electrophilic bromoacetyl bromide. The transformed fluorescent product demonstrates an emission at 340 nm after being excited at 250 nm. Significant concentration-dependent fluorescence enhancement was obtained enabling histamine determination. The procedures were examined for accuracy, precision, selectivity, and robustness in line with the ICH M10 recommendations. The method exhibits a lower limit of quantification at 0.25 ng/mL and dynamic detection throughout a linearity range of 1-200 ng/mL, providing accurate assessment of histamine in the plasma matrix.

Innovative spectrofluorometric method for determination of harmaline and harmine in different matrices.

Harmaline and harmine are naturally occurring closely related ß-carboline alkaloids found in Peganum and Banisteriopsis plants. They have historical significance in traditional practices due to their potential psychoactive and therapeutic properties. Herein, a highly sensitive spectrofluorometric method was developed for the quantifying of harmaline and harmine in diverse matrices, including pure forms, seed samples, and spiked plasma. The procedures lie in addressing the challenge of overlapping fluorescence spectra exhibited by harmaline and harmine through the incorporation of hydroxypropyl-ß-cyclodextrin, altering their chemical properties and fluorescence characteristics. Synchronous fluorescence measurements coupled with first derivative mathematical technique make it possible to distinguish between the harmaline and harmine at 419 and 456 nm, respectively. The method effectiveness is demonstrated through spectral analysis, optimization of the measurement conditions, adopting validation parameters and application to the pure form, seed samples and spiked human plasma. This methodology facilitates accurate determination of these alkaloids over the concentration range of 10─200 ng/mL. Thus, the developed approach provides a robust mean for the precise determination of harmaline and harmine, contributing to analytical chemistry's ongoing efforts to address complex challenges in quantification across diverse matrices.

Intra Nasal Use of Ethylene Diamine Tetra Acetic Acid for Improving Olfactory Dysfunction Post COVID-19.

BACKGROUND: COVID-19 has been associated with olfactory dysfunction in many infected patients. The rise of calcium levels in the nasal secretions plays an essential role in the olfaction process with a desensitization effect on the olfactory receptor neurons and a negative impact on the olfaction transmission. Ethylene diamine tetra acetic acid (EDTA) is a chelating agent that can bind free calcium in the nasal secretions, thereby reducing the adverse effects of calcium on olfactory function. OBJECTIVES: The objective of this work is to demonstrate the effect of intranasal EDTA on improving olfactory dysfunction following COVID-19. METHODS: Fifty patients with a history of COVID-19 and olfactory dysfunction that persisted for more than 6 months were enrolled in the current prospective randomized clinical trial. Participants were randomized into 2 equal groups. Twenty-five patients were treated with olfactory training only, while the remaining 25 patients received treatment with olfactory training and a topical nasal spray of ethylene diamine tetra acetic acid. The olfactory function was assessed before treatment and 3 months later using the Sniffin' Sticks test. Additionally, the determination of calcium level in the nasal secretions was performed using an ion-selective electrode before treatment and 3 months later. RESULTS: Eighty-eight percent of the patients treated with olfactory training in addition to EDTA exhibited clinical improvement, while 60% showed improvement in patients treated with olfactory training only. Furthermore, a significant decrease in the measured calcium level in the nasal secretions was demonstrated after the use of ethylene diamine tetra compared to patients treated with olfactory training only. CONCLUSION: Ethylene diamine tetra acetic acid may be associated with an improvement of the olfactory function post-COVID-19.

Higher sensitive selective spectrofluorometric determination of ritonavir in the presence of nirmatrelvir: application to new FDA approved co-packaged COVID-19 pharmaceutical dosage and spiked human plasma.

BACKGROUND: Ritonavir was recently combined with nirmatrelvir in a new approved co-packaged medication form for the treatment of COVID-19. Quantitative analysis based on fluorescence spectroscopy measurement was extensively used for sensitive determination of compounds exhibited unique fluorescence features. OBJECTIVE: The main objective of this work was to develop higher sensitive cost effective spectrofluorometric method for selective determination of ritonavir in the presence of nirmatrelvir in pure form, pharmaceutical tablet as well as in spiked human plasma. METHODS: Ritonavir was found to exhibit unique native emission fluorescence at 404 nm when excited at 326 nm. On the other hand, nirmatrelvir had no emission bands when excited at 326 nm. This feature allowed selective determination of ritonavir without any interference from nirmatrelvir. The variables affecting fluorescence intensity of ritonavir were optimized in terms of sensitivity parameters and principles of green analytical chemistry. Ethanol was used a green solvent which provided efficient fluorescence intensity of the cited drug. RESULTS: The method was validated in accordance with the ICH Q2 (R1) standards in terms of linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy, precision and specificity. The described method was successfully applied for ritonavir assay over the concentration range of 2.0-20.0 ng/mL. CONCLUSION: Ritonavir determination in the spiked human plasma was successfully done with satisfactory accepted results.

Adjusted green spectrophotometric determination of favipiravir and remdesivir in pharmaceutical form and spiked human plasma sample using different chemometric supported models.

The environmentally friendly design of analytical methods is gaining interest in pharmaceutical analysis to reduce hazardous environmental impacts and improve safety and health conditions for analysts. The adaptation and integration of chemometrics in the development of environmentally friendly analytical methods is strongly recommended in the hope of promising benefits. Favipiravir and remdesivir have been included in the COVID-19 treatment guidelines panel of several countries. The main objective of this work is to develop green, tuned spectrophotometric methods based on chemometric based models for the determination of favipiravir and remdesivir in spiked human plasma. The UV absorption spectra of favipiravir and remdesivir has shown overlap to some extent, making simultaneous determination difficult. Three advanced chemometric models, classical least squares, principal component regression, and partial least squares, have been developed to provide resolution and spectrophotometric determination of the drugs under study. A five-level, two-factor experimental design has been used to create the described models. The spectrally recorded data of favipiravir and remdesivir has been reviewed. The noise region has been neglected as it has a negative impact on the significant data. On the other hand, the other spectral data provided relevant information about the investigated drugs. A comprehensive evaluation and interpretation of the results of the described models and a statistical comparison with accepted values have been considered. The proposed models have been successfully applied to the spectrophotometric determination of favipiravir and remdesivir in pharmaceutical form spiked human plasma. In addition, the environmental friendliness of the described models was evaluated using the analytical eco-scale, the green analytical procedure index and the AGREE evaluation method. The results showed the compliance of the described models with the environmental characteristics.

Quantitative analysis of two COVID-19 antiviral agents, favipiravir and remdesivir, in spiked human plasma using spectrophotometric methods; greenness evaluation.

Favipiravir and remdesivir have been included in the COVID-19 treatment guidelines panel of several countries. The main objective of the current work is to develop the first validated green spectrophotometric methods for the determination of favipiravir and remdesivir in spiked human plasma. The UV absorption spectra of favipiravir and remdesivir have shown some overlap, making simultaneous determination difficult. Due to the considerable overlap, two ratio spectra manipulating spectrophotometric methods, namely, ratio difference and the first derivative of ratio spectra, enabled the determination of favipiravir and remdesivir in their pure forms and spiked plasma. The ratio spectra of favipiravir and remdesivir were derived by dividing the spectra of each drug by the suitable spectrum of another drug as a divisor to get the ratio spectra. Favipiravir was determined by calculating the difference between 222 and 256 nm of the derived ratio spectra, while calculating the difference between 247 and 271 nm of the derived ratio spectra enabled the determination of remdesivir. Moreover, the ratio spectra of every drug were transformed to the first order derivative using ∆λ = 4 and a scaling factor of 100. The first-order derivative amplitude values at 228 and 251.20 nm enabled the determination of favipiravir and remdesivir, respectively. Regarding the pharmacokinetic profile of favipiravir (Cmax 4.43 µg/mL) and remdesivir (Cmax 3027 ng/mL), the proposed methods have been successfully applied to the spectrophotometric determination of favipiravir and remdesivir in plasma matrix. Additionally, the greenness of the described methods was evaluated using three metrics systems: the national environmental method index, the analytical eco-scale, and the analytical greenness metric. The results demonstrated that the described models were in accordance with the environmental characteristics.

Green-adapted spectrophotometric determination of fostemsavir based on selective bromophenol blue extraction; reduction of hazardous consumption using computational calculations.

A computationally-assisted and green spectrophotometric method has been developed for the determination of fostemsavir, a recently FDA-approved drug used in combination with antiretroviral drugs to treat multidrug-resistant HIV-1 infection. The method was developed using computational studies and solvent selection based on green chemistry principles. The density functional theory method was employed to identify bromophenol blue as the preferred acid dye for efficient extraction of fostemsavir. The solvent selection process involved a careful evaluation of the green ranking of solvents, which led to the use of water as the solvent. The method involved the extraction of fostemsavir with bromophenol blue to form a yellow ion-pair complex, which exhibited maximally sharp peaks at 418 nm, enabling sensitive visible spectrophotometric determination of fostemsavir in bulk and pharmaceutical preparations. The extraction procedures were optimized, and the method was demonstrated to be sensitive over the concentration range of 2-12 µg/mL fostemsavir. Furthermore, the method was evaluated with respect to green chemistry principles using the analytical eco-scale, the green analytical method index, and analytical greenness metric approach, all of which confirmed that the data obtained by the proposed method were environmentally acceptable.

Synchronous spectrofluorimetric determination of favipiravir and aspirin at the nano-gram scale in spiked human plasma; greenness evaluation.

Favipiravir and aspirin are co-administered during COVID-19 treatment to prevent venous thromboembolism. For the first time, a spectrofluorometric method has been developed for the simultaneous analysis of favipiravir and aspirin in plasma matrix at nano-gram detection limits. The native fluorescence spectra of favipiravir and aspirin in ethanol showed overlapping emission spectra at 423 nm and 403 nm, respectively, after excitation at 368 nm and 298 nm, respectively. Direct simultaneous determination with normal fluorescence spectroscopy was difficult. The use of synchronous fluorescence spectroscopy for analyzing the studied drugs in ethanol at Δλ = 80 nm improved spectral resolution and enabled the determination of favipiravir and aspirin in the plasma matrix at 437 nm and 384 nm, respectively. The method described allowed sensitive determination of favipiravir and aspirin over a concentration range of 10-500 ng/mL and 35-1600 ng/mL, respectively. The described method was validated with respect to the ICH M10 guidelines and successfully applied for the simultaneous determination of the mentioned drugs in pure form and in the spiked plasma matrix. Moreover, the compliance of the method with the concepts of environmentally friendly analytical chemistry was evaluated using two metrics, the Green Analytical Procedure Index and the AGREE tool. The results showed that the described method was consistent with the accepted metrics for green analytical chemistry.

Simultaneous green TLC determination of nirmatrelvir and ritonavir in the pharmaceutical dosage form and spiked human plasma.

Quantitative analysis of pharmaceutical compounds up to Nano gram levels is highly recommended to introduce feasible and sensitive tool for determination of the compounds in the pharmaceutical and biological samples. Nirmatrelvir plus ritonavir was recently approved in the US, the UK and Europe as a new co-packaged dosage form for the treatment of COVID-19. The objective of this work was to develop a more sensitive TLC method based on using ß-cyclodextrin as a chiral selector additive in the mobile phase for simultaneous determination of nirmatrelvir and ritonavir in pure form, pharmaceutical formulation and spiked human plasma. The analysis procedures were developed using TLC aluminum silica gel plates and methanol-water- 2% urea solution of ß-cyclodextrin (40:10:.5, by volume) as a mobile phase with UV detection at 215 nm. The developed method was successfully applied over a linearity range of 10-50 ng/band for both nirmatrelvir and ritonavir. The method was validated for limits of detection and quantitation, accuracy, precision, specificity, system suitability, and robustness. Furthermore, the eco-friendliness of the proposed method was assessed using the analytical eco-scale and the green analytical procedure index. The described method exhibited compliance with green analytical chemistry principles based on common green metric values.

Efficacy of pentasodium diethylenetriamine pentaacetate in ameliorating anosmia post COVID-19.

BACKGROUND: COVID-19 has been frequently demonstrated to be associated with anosmia. Calcium cations are a mainstay in the transmission of odor. One of their documented effects is feedback inhibition. Thus, it has been advocated that reducing the free intranasal calcium cations using topical chelators such as pentasodium diethylenetriamine pentaacetate (DTPA) could lead to restoration of the olfactory function in patients with post-COVID-19 anosmia. METHODOLOGY: This is a randomized controlled trial that investigated the effect of DTPA on post-COVID-19 anosmia. A total of 66 adult patients who had confirmed COVID-19 with associated anosmia that continued beyond three months of being negative for SARS-CoV-2 infection. The included patients were randomly allocated to the control group that received 0.9 % sodium chloride-containing nasal spray or the interventional group that received 2 % DTPA-containing nasal spray at a 1:1 ratio. Before treatment and 30 days post-treatment, the patients' olfactory function was evaluated using Sniffin' Sticks, and quantitative estimation of the calcium cations in the nasal mucus was done using a carbon paste ion-selective electrode test. RESULTS: Patients in the DTPA-treated group significantly improved compared to the control group in recovery from functional anosmia to hyposmia. Additionally, they showed a significant post-treatment reduction in the calcium concentration compared to the control group. CONCLUSION: This study confirmed the efficacy of DTPA in treating post-COVID-19 anosmia.

Adjusted green HPLC determination of nirmatrelvir and ritonavir in the new FDA approved co-packaged pharmaceutical dosage using supported computational calculations.

The greening of analytical methods has gained interest in the quantitative analysis field to reduce environmental impact and improve safety health conditions for analysts. Nirmatrelvir plus ritonavir is a new FDA approved co-packaged medication developed for the treatment of COVID-19. The aim of this research was to develop green fitted HPLC method using pre experimental computational testing of different stationary phases as well as selecting mobile phase regarding to green analytical chemistry principles. Computational study was designed to test the physical interaction between nirmatrelvir and ritonavir and different columns (C8, C18, Cyano column). The study showed that the C18 column was better for simultaneous HPLC analysis of the cited drugs. Regarding to green point of view, mobile phase consisted of ethanol: water (80:20, v/v) provided an efficient chromatographic separation of nirmatrelvir and ritonavir within a short analytical run time, reasonable resolution and excellent sensitivity. Isocratic elution was performed on a selected C18 column and a green adjusted mobile phase at flow rate of 1 mL/min and UV detection at 215 nm. The chromatographic system allowed complete baseline separation with retention times of 4.9 min for nirmatrelvir and 6.8 min for ritonavir. The method succeeded to determine nirmatrelvir and ritonavir over the concentration range of 1.0-20.0 µg/mL in the pure form and in pharmaceutical dosage form. Greenness profiles of the applied HPLC method was assessed using analytical eco-scale, the green analytical procedure index and the AGREE evaluation method. The results revealed adherence of the described method to the green analytical chemistry principles. The authors hope to provide a promising challenge for achieving green goals through integrating computational tools and applying them with green assessment metrics.

Green fitted second derivative synchronous spectrofluorometric method for simultaneous determination of remdesivir and apixaban at Nano gram scale in the spiked human plasma.

Remdesivir and apixaban have been included in the treatment guidelines of several countries for severe COVID-19 infections. To date, no analytical method has been developed for the determination of remdesivir and apixaban in plasma matrix. The main objective of this work was to develop a highly sensitive, green-adapted spectrofluorometric method for the determination of remdesivir and apixaban at the Nanoscale. Remdesivir and apixaban showed overlapping fluorescence emission spectra at 403 nm and 456 nm when excited at 246 nm and 285 nm, respectively. This overlap was resolved in two steps. The first step was synchronous fluorescence scanning of remdesivir and apixaban, and the second step was manipulation of the second-order derivative for the obtained spectra. These steps allowed complete resolution of the overlapping fluorescence spectra and selective determination of remdesivir and apixaban at 410 and 469 nm, respectively. The variables affecting the synchronous scanning of the aforementioned drugs were optimized in terms of sensitivity parameters and principles of green analytical chemistry. The described method allowed sensitive determination of remdesivir and apixaban over the concentration range of 5-200 ng/mL and 50-3000 ng/mL, respectively. The described method was validated and successfully applied for the simultaneous determination of the mentioned drugs in pure form and in spiked human plasma.

Spectrophotometric Quantitative Analysis of Aspirin and Vonoprazan Fumarate in Recently Approved Fixed-Dose Combination Tablets Using Ratio Spectra Manipulating Tools.

BACKGROUND: Low-dose aspirin (ASP) is prescribed to millions of people around the world as a secondary preventative strategy for the majority of significant cardiovascular events; however, it carries a substantial risk of gastric ulcer and bleeding. Cabpirin® tablets, which include low-dose ASP and vonoprazan fumarate (VON), are approved in Japan for the treatment of acid-related diseases in patients who require a low dose of ASP but are at risk of ASP-associated gastric ulcers. OBJECTIVE: This paper describes the first published quantitative analytical approaches for the determination of ASP and VON. METHOD: The normal ultraviolet absorption spectra of ASP and vonoprazan overlap significantly. The ratio spectra of the studied drugs were created and manipulated by ratio difference (RD) and first derivative of ratio spectra approaches. In the RD approach, the differences in the amplitude values between 229 and 283 nm enabled the quantitative analysis of ASP, and the differences in the amplitude values between 255 and 212 nm enabled the quantitative analysis of vonoprazan. In the first derivative of the ratio spectra approach, the created ratio spectra of each drug were transformed to the first-order derivative. ASP could be determined selectively at 237.40 nm without interference from vonoprazan. Moreover, vonoprazan could be determined selectively at 244 nm without interference from ASP. RESULTS: The applied approaches were validated according to the ICH guideline, with good results. Linear correlations were obtained for ASP and vonoprazan over concentration ranges of 2-25 and 1-10 µg/mL, respectively. CONCLUSIONS: The described methods were optimized, validated, and applied for determination of the studied drugs in the synthetic mixtures and in pharmaceutical tablets without interferences. HIGHLIGHTS: Two spectrophotometric ratio spectra manipulating approaches were developed for the determination of the ASP and vonoprazan in their pharmaceutical combination tablets.

Green adherent spectrophotometric determination of molnupiravir based on computational calculations; application to a recently FDA-approved pharmaceutical dosage form.

Molnupiravir is an oral antiviral drug developed to provide significant benefit in reducing hospitalizations or deaths in mild COVID-19. Integrated green computational spectrophotometric method was developed for the determination of molnupiravir. Theoretical calculations were performed to predict the best coupling agent for efficient diazo coupling of molnupiravir. The binding energy between molnupiravir and various phenolic coupling agents, α-naphthol, ß-naphthol, 8-hydroxyquinoline, resorcinol, and phloroglucinol, was measured using Gaussian 03 software based on the density functional theory method and the basis set B3LYP/6-31G(d). The results showed that the interaction between molnupiravir and 8-hydroxyquinoline was higher than that of other phenolic coupling agents. The method described was based on the formation of a red colored chromogen by the diazo coupling of molnupiravir with sodium nitrite in acidic medium to form a diazonium ion coupled with 8-hydroxyquinoline. The absorption spectra showed maximum sharp peaks at 515 nm. The reaction conditions were optimized. Beer's law was followed over the concentration range of 1-12 µg/ml molnupiravir. Job's continuous variation method was developed and the stoichiometric ratio of molnupiravir to 8-hydroxyquinoline was determined to be 1:1. The described method was successfully applied to the determination of molnupiravir in pure form and in pharmaceutical dosage form. The results showed that the proposed method has minimal environmental impact compared to previous HPLC method.

Different spectrophotometric methods for simultaneous determination of lesinurad and allopurinol in the new FDA approved pharmaceutical preparation; additional greenness evaluation.

Lesinurad and allopurinol have been formulated in a combined dosage form providing a new challenge for the treatment of gout attacks. Two mathematical based spectrophotometric methods, area under the curve, and artificial neural networks have been developed for simultaneous determination of lesinurad and allopurinol in pure form and in combined pharmaceutical dosage form. Area under the curve has been utilized to resolve the spectral overlap between lesinurad and allopurinol. Values of area under the curve and area absorptivity were measured at two selected wavelength ranges of 242-250 nm and 255-265 nm. Two mathematically constructed equations have been used to determine the concentrations of the drugs under the study. Advanced chemometry based model, artificial neural network, has been developed utilizing the UV spectral data of lesinurad and allopurinol through various defined steps. A five-level, two-factor experimental design was used to construct 25 mixtures. Thirteen mixtures were used to set up the calibration model and 12 mixtures were used to construct a validation set. The artificial neural network model was optimized to enable precise spectrophotometric determination of the drugs under the study. The described mathematically bases spectrophotometric methods have been successfully applied to the determination of lesinurad and allopurinol in the new combined, Duzallo® tablets. Furthermore, the greenness of the described methods was assessed using four different tools namely, the national environmental method index, the analytical eco-scale, the green analytical procedure index and the AGREE evaluation method. The proposed methods showed more adherence to the greenness characters in comparison to the previously reported HPLC method.