Spider chart, greenness and whiteness assessment of experimentally designed multivariate models for simultaneous determination of three drugs used as a combinatory antibiotic regimen in critical care units: Comparative study.

In this study, five earth-friendly spectrophotometric methods using multivariate techniques were developed to analyze levofloxacin, linezolid, and meropenem, which are utilized in critical care units as combination therapies. These techniques were used to determine the mentioned medications in laboratory-prepared mixtures, pharmaceutical products and spiked human plasma that had not been separated before handling. These methods were named classical least squares (CLS), principal component regression (PCR), partial least squares (PLS), genetic algorithm partial least squares (GA-PLS), and artificial neural network (ANN). The methods used a five-level, three-factor experimental design to make different concentrations of the antibiotics mentioned (based on how much of them are found in the plasma of critical care patients and their linearity ranges). The approaches used for levofloxacin, linezolid, and meropenem were in the ranges of 3-15, 8-20, and 5-25 µg/mL, respectively. Several analytical tools were used to test the proposed methods' performance. These included the root mean square error of prediction, the root mean square error of cross-validation, percentage recoveries, standard deviations, and correlation coefficients. The outcome was highly satisfactory. The study found that the root mean square errors of prediction for levofloxacin were 0.090, 0.079, 0.065, 0.027, and 0.001 for the CLS, PCR, PLS, GA-PLS, and ANN models, respectively. The corresponding values for linezolid were 0.127, 0.122, 0.108, 0.05, and 0.114, respectively. For meropenem, the values were 0.230, 0.222, 0.179, 0.097, and 0.099 for the same models, respectively. These results indicate that the developed models were highly accurate and precise. This study compared the efficiency of artificial neural networks and classical chemometric models in enhancing spectral data selectivity for quickly identifying three antimicrobials. The results from these five models were subjected to statistical analysis and compared with each other and with the previously published ones. Finally, the whiteness of the methods was assessed by the recently published white analytical chemistry (WAC) RGB 12, and the greenness of the proposed methods was assessed using AGREE, GAPI, NEMI, Raynie and Driver, and eco-scale, which showed that the suggested approaches had the least negative environmental impact. Furthermore, to demonstrate solvent sustainability, a greenness index using a spider chart methodology was employed.

Eco-friendly micellar HPLC approach for simultaneous estimation of combination therapy for hidradenitis suppurativa: Applications to spiked human plasma and different dosage forms.

This study introduces a new method for analyzing rifampicin, moxifloxacin, and metronidazole using a green micellar High Performance Liquid Chromatography-Ultraviolet method in bulk drugs, different commercial formulations, and spiked human plasma. The combined therapy of these three broad-spectrum antibiotics is used to cure refractory hidradenitis suppurativa (HS), an inflammatory condition affecting the skin. The sustainable separation was attained on a reversed-phase C18 Kinetex® column maintained at ambient temperature in less than 5 min. The mobile phase comprises 0.1 M sodium dodecyl sulfate (SDS) in water, pH 3.5, adjusted using o-phosphoric acid, and 10% n-butanol. The flow rate was 1 mL/min, with 10 µL injection volume and UV detection at 230 nm. The impact of three key significant variables, SDS concentration, n-butanol percentage, and the mobile phase pH, on suitability parameters was studied. ICH and FDA guidelines were committed to when validating the technique. The results showed linear calibration graphs with high precision and accuracy, in both pure and spiked plasma. The method is efficient, easy to use, and has a high sample throughput, making it suitable for routine analysis in the quality control department and therapeutic monitoring. It is also evaluated as a green-and-white substitute for traditional reported methods.

A validated eco-friendly HPLC-FLD for analysis of the first approved antiviral remdesivir with other potential add-on therapies for COVID-19 in human plasma and pharmaceuticals.

It is crucial to have a reliable and sensitive method for separating common drugs used in SARS-CoV-2 pneumonia treatment protocols for ongoing treatment and upcoming investigations. This study presents an HPLC-FLD approach to analyze three co-administered medicines - remdesivir (RDV), hydroxychloroquine sulphate (HCQ), and levofloxacin hemihydrate (LVX) - in their pure forms, pharmaceutical preparations, and spiked human plasma. The HPLC-FLD analysis was conducted using a Symmetry® C18 column (100 mm × 4.6 mm ID, 3.5 µm particle size) at 40 °C, with (A) an aqueous mixture of 0.02 M phosphate buffer and 0.2% heptane-1-sulphonic acid sodium solutions (50 : 50) adjusted to pH 3, (B) acetonitrile, and (C) methanol as the mobile phase. The injection volume was 10 µL, and the flow rate was 1.5 mL min-1. The detection was done using a multi-wavelength excitation and emission fluorescence detector, with individual optimization for each drug. The drug separation time was less than 10 minutes, and the method showed sensitive and wide linearity ranges for all medicines, with r2 values of more than 0.999. The impact of the mobile phase pH and flow rate on suitability parameters (retention time and number of theoretical plates) was studied. The method was found to be environmentally friendly based on GAPI and AGREE metrics. The validity of the method was evaluated following ICH and FDA guidelines.

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.

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.

Validated Stability-Indicating Methods for Determination of Mometasone Furoate in Presence of its Alkaline Degradation Product.

Two novel stability-indicating TLC densitometric and chemometric methods were developed for the determination of mometasone furoate (MF) in the presence of its alkaline degradation product (MF Deg). The developed TLC densitometric method (Method A) is based on the quantitative densitometric separation of MF from its alkaline degradation product on silica gel 60 F254 and measurement of the bands at 250 nm. The separation was carried out using hexane-chloroform-methanol-acetonitrile (6:6:1:0.3, by volume) as a developing system. A well-resolved and compact bands for (MF) and (MF Deg) at retention factors 0.36 and 0.66, respectively. Good resolution between (MF) and (MF Deg) assured the specificity of the proposed method. The method showed good linearity in the concentration range 0.5-5 µg/band with r2 = 0.9998. The method validation was performed according to ICH guidelines demonstrating to be accurate, precise, robust and sensitive. The LOD and LOQ were found to be 0.21 and 0.63 µg/band for MF, respectively. The developed TLC-densitometric method can be applied for identification and quantitative determination of MF in bulk drug and pharmaceutical dosage forms without any interference from excipients and degradates. Method B is a multivariate chemometric-assisted spectrophotometry, where classical least squares, principal component regression and partial least squares were applied. Statistical analysis of the results has been carried out revealing high accuracy and good precision.