Green Analytical Procedure Index Research Articles

Chromatographic assay of recently approved co-formulation of Vonoprazan fumarate with low dose Aspirin: AGREE, Complex MoGAPI, and RGB 12-model assessments.

Two simple, valid and green chromatographic based techniques are developed in the present work for first time to simultaneously analyze the recently approved combination of Aspirin (ASP) with the novel gastro-protective agent Vonoprazan (VON). First method is an HPLC-DAD "diode array detection", where separation was successful using C18 (250 × 4.6mm) column with isocratic elution of phosphate buffer-pH 6.8 and acetonitrile in ratio of 63:37 with detection at 230nm. Second method is an HPTLC method on HPTLC silica plates using ethyl acetate: ethanol (75%): ammonia (5:5:0.05 v/v) mobile phase followed by densitometric scanning at 230nm. The methods were applied successfully for analysis of VON and ASP mixture in laboratory-prepared tablets and the methods were validated in regards to linearity, precision, accuracy and selectivity. The proposed methods are assessed for their greenness and whiteness as well using the "Analytical GREEnness Metric Approach", "Complementary Modified Green Analytical Procedure Index" and the new algorithm "RGB 12 model" (Red-Green-Blue) and proved the greenness and the sustainability of the methods in the routine assay of the newly marketed formulation.

Eco-Friendly Synchronous Spectrofluorimetric Determination of Imipenem, Cilastatin, and Relebactam; Application to Market Formulations and Biological Fluids; Greenness Assessment.

The proposed study introduces a rapid, sensitive, and simple synchronous spectrofluorimetric technique for simultaneous quantification of relebactam, cilastatin, and imipenem in marketed pharmaceutical forms and biological fluids. Using synchronous fluorescence spectroscopy at Δ λ = 110nm, cilastatin was detected at 360nm. Fourier Self-Deconvolution was subsequently applied to the spectrum to estimate relebactam and imipenem at 430nm and 470nm, respectively after detection of cilastatin at 360nm ensuring no cross-interference. The pH was adjusted to 8.0 using 2.0 mL of alkaline borate buffer. This approach allowed for the precise quantification of relebactam, cilastatin, and imipenem through ranges of 50-400 ng mL- 1, 20-500 ng mL- 1, and 50-500 ng mL- 1 respectively. The lower detection and quantitation limits were 9.9 and 29.7 ng mL- 1 for REL, 4.5 and 13.6 ng mL- 1 for CIL and 5.5 and 16.5 ng mL- 1 for IMP. The proposed method was successfully applied for the determination of studied drugs in their pharmaceutical formulations with a high degree of accuracy and without interference from common excipients. This approach allowed for the precise quantification of relebactam, cilastatin, and imipenem through ranges of 50-400 ng mL- 1, 20-500 ng mL- 1, and 50-500 ng mL- 1, respectively. The proposed method was rigorously validated according to ICH guidelines. Furthermore, the method's environmental impact was assessed using Eco-scale and Green Analytical Procedure Index (GAPI) techniques.

Innovative anti-proliferative effect of the antiviral favipiravir against MCF-7 breast cancer cells using green nanoemulsion and eco-friendly assessment tools.

Telomerase enzyme prevents telomere shortening during division, having human telomerase reverse transcriptase (hTERT) as its catalytic subunit. Favipiravir (FAV), an RNA-dependent RNA polymerases inhibitor, shared structural similarity with hTERT and thus assumed to have cytotoxic effect on cancer cells, in addition to its prophylactic effect to immunocompromised cancer patients. Nanoemulsion (NE) is a potential tumor cells targeting delivery system, thereby enhancing therapeutic efficacy at the intended site, mitigating systemic toxicity, and overcoming multidrug resistance. The objective of this study is to develop a green FAV nanoemulsion (FNE) that is environmentally friendly and safe for patients, while aiming to enhance its cytotoxic effects. The study also highlights the environmental sustainability of the developed RP-HPLC method and assesses its greenness impact. The FNE formulation underwent thermodynamic stability testing and invitro characterization. Greenness was assessed using advanced selected tools like the Analytical Eco-Scale (AES), Analytical Greenness Metric for Sample Preparation (AGREEprep), and green analytical procedure index (GAPI). The cytotoxic potential of FNE was screened against MCF-7 breast cancer and Vero normal cell lines using SRB assay. Stable and ecofriendly FNE was formulated having a particle size (PS) of 25.29 ± 0.57nm and a zeta potential of -6.79 ± 5.52 mV. The cytotoxic effect of FNE on MCF-7 cells was more potent than FAV with lower IC50 while FNE showed non-toxic effect on VERO normal cell line. Therefore, the FAV nanoemulsion formulation showed targeted cytotoxicity on MCF-7 cells while being non-toxic on normal Vero cells.

Eco-friendly RP-HPLC approach for simultaneously estimating the promising combination of pentoxifylline and simvastatin in therapeutic potential for breast cancer: Appraisal of greenness, whiteness, and Box–Behnken design

Abstract Breast cancer affects millions of women worldwide. This study explores the potential of combining pentoxifylline (PTX) and simvastatin (SIM) as a treatment for breast cancer. We aimed to develop six sustainability tools using green and white metrics to evaluate the environmental impact of reversed-phase high-performance liquid chromatography (RP-HPLC) methods for analyzing and separating PTX and SIM in their pure forms. The tools include analytical GREEnness, green analytical procedure index, Complexgreen analytical procedure index, analytical greenness metric for sample preparation, blue applicability grade index, and the RGB 12 algorithm. For the separation, we used a Novapack C8 column (15 × 0.46 cm, 5 µm) at 25°C. The injection volume was 5.0 µL, the wavelength was set to 210 nm, and the total runtime was 5 min. We identified optimal chromatographic conditions efficiently using the Box–Behnken design with minimal trials. We investigated the effects of three factors on retention time and resolution: acetonitrile ratio, pH, and flow rate. We used overlay plots with a 60:40 ratio (v/v) of acetonitrile and bi-distilled water to forecast the most effective mobile phase. The calibration curves for PTX and SIM showed a correlation value of over 0.999 within the range of 5–60 µg·mL−1. The recovery rates ranged from 99.9% to 100.2%, indicating high accuracy. Our RP-HPLC technique proves to be reliable and efficient for the simultaneous estimation of multiple anticancer drugs. We evaluated the environmental sustainability of this approach using green and white metrics, and the recommended method has been thoroughly validated according to International Council for Harmonisation guidelines, making it highly reliable for analyzing new formulations.

Feasible synthesis and physicochemical features of a luminescent cadmium-metal organic frameworks (Cd-MOFs) composite, and its functionalization as a turn-off sensor towards selective determination of bisphenol A in food, water, and paper products

In the current study, a cadmium-metal organic frameworks (Cd-MOFs) structure was developed using a chemical process. The work comprised two main stages, initially inspection of the physicochemical features of the structure, and secondly, the application of the prepared Cd-MOFs as a turn-off nanosensor for the spectrofluorimetric determination of bisphenol A (BPA). Field emission scanning electron microscopy (FESEM) revealed the morphological features with the flake-like resembled shape. The elemental peaks for C, O, N, S, and Cd were residing as demonstrated by the energy-dispersive X-ray (EDX) results. The nonporous structure with a surface area of 25 cc/g was determined through the BET surface area results. The fluorescence spectra of Cd-MOFs demonstrated fluorescence emission at 470 nm after excitation at 320 nm. The quenching of the native fluorescence of Cd-MOFs was quantitatively and selectively produced by increasing concentrations of BPA. Therefore, Cd-MOFs have been applied as a turn-off nanosensor for the spectrofluorimetric determination of BPA, for the first time. The proposed approach validates linearity over the concentration range of 0.05–1.0 µg/mL with a detection limit of 0.01 µg/mL, signifying the method’s high sensitivity. Detection of low concentrations of BPA allowed for the real sample analysis in the food industries, including orange juice, tap water, infant feeding bottles, and food contact sheets. Moreover, The excellent eco-friendliness and greenness of the established approach were verified by employing the Analytical GREEnness (AGREE) and complementary Green Analytical Procedure Index (ComplexGAPI). The RGB 12 algorithm has functioned to prove the proposed method is greener, whiter, more sustainable, analytically effective, and less expensive than the reported ones. The proposed approach was validated according to ICH guidelines. This method presents a hopeful approach to quickly and accurately detect and quantify BPA in the food industry, which reinforces food safety and guards consumers’ health.

Sustainable and efficient monitoring of tryptophan and tyrosine serum levels: a green HPTLC method as a biomarker for type 2 diabetes

In recent years, there has been considerable interest in using amino acids like tryptophan (Trp) and tyrosine (Tyr) as biomarkers for various diseases, including type 2 diabetes mellitus (T2D). In diseases like T2D, the metabolism of Trp and Tyr is altered. The activity of enzymes involved in Trp metabolism increases, leading to a decrease in its serum level. On the other hand, the serum level of Tyr increases due to the suppressed activity of its metabolizing enzymes. These observations suggest that Trp and Tyr metabolism may play a crucial role in the pathophysiology of type 2 diabetes. Our study highlights the potential utility of Trp and Tyr as biomarkers for the early detection, prognosis, and monitoring of this metabolic disorder. Given these observations, we aimed to develop a high-performance thin-layer chromatographic (HPTLC) method that is sensitive, selective, rapid, and environmentally friendly for estimating the concentrations of Trp and Tyr in biological fluids, particularly serum samples. To evaluate the method, we performed analysis using serum samples from controlled and streptozotocin-induced diabetic rats. Our main objective was to develop a method that is sensitive and selective for precisely determining Trp and Tyr serum levels, which could serve as potential biomarkers for T2D. Fluorescence and absorption modes were employed for densitometry scanning. We assessed the precision and high separation efficiency of the chromatographic system by calculating parameters such as separation and resolution factors, number of theoretical plates, and height equivalent to theoretical plates. To evaluate the environmental impact of our proposed method, we employed the AGREE (Analytical GREEnness metric) and GAPI (Green Analytical Procedure Index) greenness assessment tools. The results confirmed that our method is environmentally friendly and exhibits superior eco-friendliness and greenness compared to other reported methods.Graphical

Utility of green chemistry for spectrofluorometric determination of fingolimod via metal complexation; Application to dosage and spiked biological fluid

The goal of the current research was to establisha quick and practical fluorimetric technique for fingolimod analysis. The approach relied on the drug's complex formation with the zinc ion to produce a high-fluorescence product. The fluorescence was further enhanced by adding sodium dodecyl sulfate, and it was observed at 325 nm following excitation at 475 nm. With a correlation coefficient of 0.9999, the association between emission intensity and fingolimod concentration was linear between 5-150 ng mL-1. The quantitation limit was 2.059 ng mL-1,while the detection limit was 0.679 ng mL-1. The buffer type, pH and concentration, type of surfactant and concentration, and finally the diluting solvent were among the reaction conditions that were closely examined. With great precision and reliability, the drug in question was quantified using this method in both spiked human plasma and capsule formulations. The proposed method's level of greenness was assessed using two methodologies: the analytical greenness metric (AGREE) and the Green Analytical Procedure Index (GAPI).

RGB Trichromatic Whiteness Assessment of Bio Analytical Chromatographic Tool Using Fluorescence for Quantitation of Semaglutide: Application to Pharmaceutical Preparations and Spiked Plasma.

Semaglutide (SEMG) is one of the most widely used and trending medications to treat type II diabetes and obesity.This work aimed to develop a liquid chromatography with spectroflourimetric detection (HPLC-flourimetry) analysis of SEMG in both its tablet dosage form and plasma. The power of fluorescence detection coupled with HPLC proved its capability as a bioanalytical tool to assay SEMG in plasma samples owing to its simplicity and sensitivity which reached below the Cmax of SEMG. Separation was done using a C18 column with mobile phase of acetonitrile and water acidified with orthophosphoric acid (pH 3.5) (1.41 × 10-5M) in isocratic mode in ratio 57:43 and 1mL/min flow rate after extraction using protein precipitation. Detection was carried out at λ excitation of 238nm and λ emission of 416 and 307nm for SEMG and the internal standard, respectively. Evaluation of greenness of the proposed method was done using AGREE (Analytical GREEnness Metric Approach), ComplexGAPI (Complementary Green Analytical Procedure Index) & the new algorithm RGB 12 model (Red-Green-Blue). They showed that these methods can be a greener alternative with acceptable sensitivity for analysis of SEMG. The developed seven min-assay was validated per ICH as well as FDA bio analytical methods' guidelines to prove its applicability for routine sample analysis and future pharmacokinetic studies.

Pioneering simultaneous determination of breast cancer medications and metformin through sustainable micellar electrokinetic chromatographic method

The current study is the first report for the capillary electrophoretic simultaneous determination of five breast cancer medications, including febuxostat, quercetin, letrozole and doxorubicin in addition to metformin which is frequently co-administered with these drugs. The studied drugs are frequently purchased in different co-formulations used for breast cancer patients. A green micellar electrokinetic chromatographic (MEKC) method is proposed and optimized assisted by factorial design. The factors optimized include pH and concentration of buffer, surfactant concentration, as well as the applied voltage and injection time. The experimental results prove the optimum separation of the five drugs at pH 9.7 and buffer concentration of 10 mM with sodium dodecyl sulfate (SDS) concentration of 40 mM with +25 kV applied voltage. The developed method is validated considering linearity, precision, accuracy, and robustness adopting official guidelines. Good linearity is observed for all drugs, with correlation coefficients greater than 0.99. The range of percentage recoveries was from 98% to 102% with less than 2% relative standard deviation demonstrating the precision and accuracy of the established method. The study includes in-vitro assay of febuxostat, metformin, and doxorubicin in spiked human plasma. In addition, Accurate determination of the analytes under study in a variety of pharmaceutical dosage forms is accomplished by application of the proposed MEKC method. The greenness profile of the investigated method is confirmed using analytical eco-scale in addition to green analytical procedure index (GAPI) approaches.

Greenness and whiteness appraisal for bioanalysis of quetiapine, levodopa and carbidopa in spiked human plasma by high performance thin layer chromatography.

A sustainable HPTLC-densitometric method was developed for quantitative determination of Quetiapine (QUET), Levodopa (LD) and Carbidopa (CD) in presence of Dopamine (DOP) as an internal standard. This applicable technique was achieved by spiking human plasma and extraction was performed using the protein precipitation approach. The mobile phase used was acetone, dichloromethane, n-butanol, glacial acetic acid and water (3: 2.5: 2: 2: 1.75, by volume). Method validation was done according to US-FDA guidelines and was able to quantify Quetiapine, Levodopa and Carbidopa in the ranges of 100-4000, 200-8000 and 30-1300 ng/mL, respectively. Bioanalytical method validation parameters were assessed for the studied drugs. Finally, the analytical suggested methodology was evaluated using various green and white analytical chemistry metrics and other tools, such as the green solvent selection tool, analytical eco-scale, green analytical procedure index, analytical greenness metric approach and the red-green-blue algorithm tool. The results revealed that the applied analytical method had a minor impact on the environment and is a relatively greener option than other previously reported chromatographic methods.

Spectrophotometric determination of olanzapine, fluoxetine HCL and its impurity using univariate and chemometrics methods reinforced by latin hypercube sampling: Validation and eco-friendliness assessments

Novel univariate and chemometrics-aided UV spectrophotometric methods were tailored to undergo the fundamentals of green and white analytical chemistry for the simultaneous estimation of a ternary mixture of olanzapine (OLA), fluoxetine HCL (FLU), and its toxic impurity 4-(Trifluoromethyl) phenol (FMP) without any prior separation. The dual-wavelength ratio spectrum univariate method was used to determine OLA and FLU in the presence of FMP in the range of (4–20) and (5–50) μg/ml, respectively. In compliance with the International Conference on Harmonization (ICH) standards, the technique was validated and established Remarkable accuracy (98–102%) and precision (< 2%) with limits of quantification (LOQs) of 0.432 and 2.002 μg/ml, respectively. Partial least squares (PLS) and artificial neural networks (ANNs) are chemometric methodologies that have advantages over the univariate method and use significant innovations employing Latin hypercube sampling (LHS), allowing the generation of a reliable validation set to guarantee the effectiveness and sustainability of these models. The concentration ranges used were (2–20), (2–20), and (5–50) μg/ml; for PLS, the LOQs were 0.602, 0.508, and 1.429 μg/ml, and the root mean square errors of prediction (RMSEPs) were 0.087, 0.048, and 0.159 for OLA, FMP, and FLU, respectively; and for ANNs, the LOQs were 0.551, 0.465, and 0.965 μg/ml, with RMSEPs of 0.056, 0.047, and 0.087 for OLA, FMP, and FLU, respectively. The developed methods yield a greener National Environmental Methods Index (NEMI) with an eco-scale assessment (ESA) score of 90 and a complementary Green Analytical Procedure Index (complex GAPI) in quadrants with an analytical greenness metric (AGREE) score of 0.8. The Red‒Green–Blue 12 algorithm (RGB 12) scored 88.9, outperforming on reported methods and demonstrating widespread practical and environmental approval. Statistical analysis revealed no noteworthy differences (P > 0.05) among the proposed and published techniques. Both pure powders and pharmaceutical capsules were analyzed via these methods.

First fluorescence method for monitoring the doping stimulant drug solriamfetol in plasma and urine: A pharmacokinetic study in volunteers’ urine with greenness, whiteness, and blueness assessments

A green, sustainable, simple, and highly sensitive spectrofluorimetric method was developed to determine solriamfetol hydrochloride for the first time in biological fluids and dosage form. To the best of our knowledge, no Fluorimetric methods have been reported for solriamfetol determination in plasma and urine. The method is based on measuring the intrinsic fluorescence of solriamfetol hydrochloride at 522 nm after excitation at 260 nm in ammonium acetate buffer solution at pH 4. All factors influencing the response have been carefully investigated. The method was linear over a concentration range of 10 to 1800 ng/mL (r = 0.9998). The limit of detection (LOD) and limit of quantification (LOQ) values were found to be 3.2 and 9.8 ng/mL, respectively, indicating the excellent sensitivity of the proposed method. The pharmaceutical dosage form, spiked human plasma, and urine samples were successfully analyzed using the described method with average recoveries of 99.79 ± 0.739, 99.27 ± 1.885, and 99.57 ± 1.701, respectively. Plasma samples were first subjected to protein precipitation using 10 % perchloric acid, while urine samples were analyzed directly without any pretreatment. Furthermore, the suggested method was applied effectively on real human volunteers’ urine to measure renal clearance, the cumulative amount of solriamfetol excreted unchanged in the urine, and the percent of the dose recovered. The eco-friendly nature and sustainability of this work were evaluated using trending greenness, whiteness, and blueness assessment metrics. The greenness assessment tools, namely the Analytical GREEnness metric tool (AGREE), Analytical Eco-scale, and complementary green analytical procedure index (complex GAPI) were selected to prove the eco-friendly nature of the method. Additionally, whiteness and blueness assessments were conducted using the Red-Green-Blue model (RGB model), and high Blue Applicability Grade Index (BAGI), respectively. The proposed method is a promising analytical tool for routine analysis in quality control labs, therapeutic drug monitoring, and pharmacokinetics studies.

Novel eco-friendly HPTLC method using dual-wavelength detection for simultaneous quantification of duloxetine and tadalafil with greenness evaluation and application in human plasma

A novel, environmentally friendly, and sensitive HPTLC method has been developed and validated for simultaneous quantification of duloxetine (DLX) and tadalafil (TDL) in their pure state, laboratory-prepared mixtures, and spiked human plasma. This method is particularly important for patients dealing with depression and sexual issues, as it allows for the measurement of these co-administered antidepressant and sexual stimulant drugs in biological fluids. The separation process employed a stationary phase of pre-coated silica gel 60 F254 and a mobile phase consisting of ethyl acetate, acetonitrile, and 33% ammonia (8:1:1, v/v). The optimized mobile phase resulted in well-defined bands for DLX and TDL, with Rf values of 0.3 and 0.8, respectively with dual-wavelength detection at 232 nm for DLX and 222 nm for TDL. Polynomial regression analysis revealed exceptional linearity for both drugs, with correlation coefficients of 0.9999 over concentration ranges of 10–900 ng/band for DLX and 10-1200 ng/band for TDL. The quantitation limits were 8.2 ng/band for DLX and 8.6 ng/band for TDL, while the detection limits (LOD) were 2.7 ng/band for DLX and 2.8 ng/band for TDL. The validation of this method followed the guidelines set by the International Council for Harmonization (ICH). Additionally, the suggested method’s greenness was assessed by means of four up-to-date ecological tools, namely the Eco-Scale, the National Environmental Method Index (NEMI), the Green Analytical Procedure Index (GAPI), and the Analytical Greenness metric approach (AGREE). The proposed method was also assessed using the Blue Applicability Grade Index (BAGI), a recently developed metric for assessing the practicality (blueness) of procedures.

Green and Sensitive Analysis of the Antihistaminic Drug Pheniramine Maleate and Its Main Toxic Impurity Using UPLC and TLC Methods, Blueness Assessment, and Greenness Assessments

For the first time, two direct and eco-friendly chromatographic approaches were adapted for the simultaneous estimation of pheniramine maleate (PAM) and its major toxic impurity, 2-benzyl pyridine (BNZ). Method A used reversed-phase ultra-performance liquid chromatography; separation was achieved within 4 min using a C18 column with a developing system of methanol/water (60:40 v/v) with a 0.1 mL/min flow rate. Photodiode array detection was adjusted at 215 nm. The method was linear in the ranges of 5.0–70.0 and 0.05–10.0 µg/mL for PAM and BNZ, correspondingly. Method B used thin-layer chromatography; separation was applied on silica gel TLC F254 using ethanol/ethyl acetate/liquid ammonia (8:2:0.1, in volumes) at room temperature, at 265 nm. Linearity was assured at concentration ranges 0.5–8.0 and 0.1–3.0 µg/band for the two components, respectively. Generally, the new UPLC and TLC methods outperform the old ones in terms of quickness, greenness, and sensitivity. Concisely, the greenness features were partially achieved using the Green Analytical Procedure Index (GAPI) and the Analytical Greenness (AGREE) pictograms. In contrast, the usefulness of the novel approaches was assured via the Blue Applicability Grade Index (BAGI) tool.

Smartphone based TLC approach versus conventional densitometric measurement for the simultaneous determination of donepezil and memantine, content uniformity testing along with greenness and whiteness assessment

Thin layer chromatography (TLC) is a straightforward and economical technique that plays a major role in analytical field. Introducing the amenities of smartphones as accessible alternative detectors to TLC separation methods elaborates the cost-effectiveness of this technique and supports the appropriate assay of various aliphatic compounds after visualization by suitable reagents. Herein, two TLC coupled with smartphone's camera approaches are proposed for the assay of donepezil hydrochloride (DON) and memantine hydrochloride (MEM), a combined medication used in the management of Alzheimer's disease. Separation was achieved using a developing system of ethyl acetate, methanol, toluene, and ammonia (33%, w/v) in a ratio of 4:1:4:0.2, by volume. The dried plates were scanned at 190 nm for the densitometric assay, then visualized with modified Dragendorff's reagent and photographed by smartphone's camera. The data were integrated by displaying the photos in either ImageJ software or Color-Picker application. The findings produced from the three detection approaches were contrasted over concentration ranges of 1–18 & 4–28 μg/spot for the densitometric method, while the range was 1–20 & 1–30 μg/spot for the ImageJ method and 3–18 & 2–20 μg/spot for the Color-Picker method for DON and MEM, respectively. The methods were suitable for assaying both drugs in their pure form and combined pharmaceutical formulations. Densitometric and ImageJ-based methods were applied to evaluate the dosage forms content uniformity. The developed methods were assessed by three metric tools for greenness and sustainability, namely Green Analytical Procedure Index, Analytical GREEnness Metric Approach, and White Analytical Chemistry.

Harnessing spectrophotometry resolution power for determining ternary mixture for respiratory disorders treatment in their pharmaceutical formulation.

A ternary mixture incorporating Hydroxyzine hydrochloride (HYX), Ephedrine hydrochloride (EPH) and Theophylline (THP) frequently prescribed for the treatment of respiratory diseases. Herein, two spectrophotometric methods are designated and applied to resolve these three components in their mixture. Method A is ratio-subtraction combined with derivative spectrophotometry, where THP can be determined directly at its λmax 271 nm (neither HYX or EPH interfere), then for determination of HYX and EPH, the ternary mixture was divided by 22 μg/mL of THP and after subtraction of the plateau region, HYX can be determined directly at its λmax 234.2 nm (absence of EPH intervention). Finally, the third derivative (3D) spectrophotometric approach was utilized to estimate EPH by detecting the peak amplitude at 222 nm with Δλ = 4 and a scaling factor 100. Principal Component Regression (PCR) and Partial Least Squares (PLS), two multivariate calibration approaches, were applied effectively in Method B. This method effectively quantified the mixture under investigation by using the absorption spectra obtained from suitable solutions of the three components in the 210-230 nm region. The calibration models were evaluated using cross-validation with PCR and PLS, producing statistical characteristics that demonstrate the effectiveness of the calibration models. Synthetic and pharmaceutical preparations were also used to conduct external validation. In pharmaceutical formulation, these methods were successfully applied to analyze HYX, EPH, and THP without overlap from formulation's excipients. Moreover, the study's findings were statistically contrasted with those of earlier reported HPLC method. Appraisal approaches were used to determine whether the new spectrophotometric methods had an adverse environmental impact involving the Green Analytical Procedure Index (GAPI) and the AGREE (Analytical Greenness). These evaluations delivered information about the methods' eco-friendliness and sustainability, proving that they are in line with ecologically attributed practices. Furthermore, the Blue Applicability Grade Index (BAGI) was utilized to identify and verify the feasibility and practicality of the suggested approaches.

Sustainable chemometric analysis of tension headache drugs in the presence of nephrotoxic impurities

A three-drug combination of caffeine, aspirin and paracetamol is widely prescribed as a first-line treatment for tension headaches and migraine attacks. Being of easy access as an over-the-counter medication, renal papillary necrosis may be caused if large doses are taken chronically. Moreover, several toxic impurities such as p-aminophenol and p-hydroxy acetophenone may be formed during the synthesis or storage of paracetamol. These impurities are classified as nephrotoxic and teratogenic materials which obliges pharmaceutical companies to develop cost-effective methodologies for their detection along with paracetamol itself. During the current study, multivariate chemometric-assisted spectrophotometric models namely; Partial Least Squares, Genetic Algorithm-Partial Least Squares and Multivariate Curve Resolution-Alternating Least Squares were developed for assaying and resolving the complex spectral overlap of the ternary combination in the presence of the nephrotoxic impurities; p-aminophenol and p-hydroxy acetophenone. A comparison was held between the three models where the optimized Genetic Algorithm-Partial Least Squares and Multivariate Curve Resolution-Alternating Least Squares models reduced the root mean square by 18.1%, 21.7%, 20.0%, 43.9% and 11.5% and 31.5%, 32.6%, 39.3%, 54.6% and 37.9% for caffeine, aspirin, paracetamol, p-aminophenol and p-hydroxy acetophenone, respectively. Panadol® migraine tablets were successfully analyzed using the constructed models without interference from the excipients. A statistical comparative analysis and greenness evaluation were carried out using two assessment tools including the “Green Analytical Procedure Index” and the “Analytical Greenness metric”. Also, the “Whiteness Analytical Chemistry tool” using the RGB12 model and the Blueness Applicability Grade Index were applied. Greener quadrants and a high score of 0.74 for the greenness tools were achieved with accepted statistical parameters regarding t and f values. Also, the high scores of the Blueness Applicability Grade Index and RGB12 metrics of 90 and 98.3, respectively confirmed the method's wide practicality and utility. Although other chemometric methods were reported for assaying the ternary combination, our developed method was the only one that incorporated toxic impurities during the analysis along with implementing greenness, whiteness and blueness assessments to ensure the method's sustainability.

Analysis of binary mixture of oxytetracycline and bromohexine in their combined veterinary formulation by four simple spectrophotometric methods with greenness assessment

Tetracyclines family is considered as the first-line antibiotic drugs for food animals. Formulating bromhexine (BR) with oxytetracycline (OTC) improved the antibacterial activity of OTC, besides it is considered as a mucolytic agent. Four precise, rapid, and simple spectrophotometric methods were successfully developed for resolution of the overlapped spectra of OTC and BR in their pure form and in their pharmaceutical formulation. The proposed methods are absorption correction (AC), dual wavelength (DW), induced dual wavelength (IDW), and spectrum subtraction (SS) spectrophotometric methods. The developed methods were used for the determination of OTC and BR in the ranges of 2–50 µg/mL and 1–30 µg/mL, respectively for all methods. For (AC) and (SS) methods, OTC and BR were determined at 380 nm and 245.6 nm, respectively after spectral resolution steps. While for (DW) method, the absorbance difference between λ (271.8 –287.6 nm) and λ (245.6 –283.2 nm) were used for the determination of OTC and BR, in order. For IDW, it depended on using the absorbance difference between 271.8 nm and 245.6 nm as well as the equality factor (F) calculated for each drug at the selected wavelengths. In all methods, HCl was used as a solvent and they are validated according to ICH guidelines. Several green metric tools have been developed to evaluate the greenness of the analytical methods like National Environmental Methods Index (NEMI), Modified NEMI, Analytical Eco-scale, Green Analytical Procedure Index (GAPI) and Analytical GREEnness calculator (AGREE), and all ensured the low impact of the suggested approaches on health and environment. The proposed methods are highly selective, robust and precise. Additionally they are time and money effective and can be used in any analytical laboratory.

A Highly Sensitive Inclusion Complex Based Spectrofluorimetric Method for the Determination of Certain Sodium Glucose Cotransporter-2 Inhibitors: Greenness Assessment and Application to Different Biological Fluids.

This study introduces a remarkably simple, green, and highly sensitive inclusion complex based spectrofluorimetric method for analyzing two sodium glucose cotransporter-2 (SGLT2) inhibitors: empagliflozin (EGF) and dapagliflozin (DGF). The method utilizes beta-cyclodextrin (β-CD) complexation to enhance the native fluorescence of EGF and DGF in aqueous solutions, resulting in 11.0-fold and 9.0-fold intensity increases, respectively. Fluorescence measurements were conducted at 301 nm emission following 230 nm excitation for both drugs. The method demonstrates excellent linearity (0.9994 for EGF and 0.9993 for DGF) over concentration ranges of 5.0-250.0 ng/mL and 10.0-300.0 ng/mL, with low detection limits of 1.05 and 1.38 ng/mL for EGF and DGF, respectively. The method's versatility was validated through successful application in pharmaceutical formulations, content uniformity testing, and biological fluids. This eco-friendly approach primarily uses water as a solvent and requires minimal reagents. The method's environmental impact was comprehensively evaluated using the analytical eco-scale, green analytical procedure index (GAPI), and analytical greenness metric (AGREE).

Chiral Separation of Racemic Atracurium through β-Cyclodextrin Sulphated Sodium Modified Gold Nanoparticles/Pencil Graphite Electrode: An Eco-Friendly Voltammetric Behavior of Cisatracurium Isomer in Real Samples

A novel electrochemical sensor for chiral separation of racemic Atracurium (racATR) into its three isomers (cis-cis, cis-trans, trans-trans) was assembled. The sensor was based on immobilization of β-cyclodextrin sulphated sodium salt (S-β-CD) with gold nanoparticles (Au-NPs) on pencil graphite electrode (S-β-CD/Au-NPs/PGE). A significant increase in peak currents of cyclic voltammetry and differential pulse voltammetry was noticed through applying this sensor. This is attributed to the electrochemical sensitivity of Au-NPs along with high chiral discrimination of S-β-CD via the host-guest interaction. The sensor's construction was tested by the electrochemical oxidation behavior of cisatracurium (cisATR) isomer in Britton Robinson buffer (pH = 11) at scan rate 30 mV s−1. The peak currents increased proportionally as the cisATR concentration varying between 8.0 × 10–8−1.0 × 10–6 M. The correlation coefficient and limit of detection have been demonstrated to be 0.9999 and 8.8 × 10–9, respectively. The analytical applications of S-β-CD/Au-NPs/PGE electrode were assessed through the dosage form and human plasma as a real sample. The proposed method was found to be an eco-friendly electrochemical approach according to the four greenness assessment tools: Analytical Eco-Scale, National Environmental Method Index, Green Analytical Procedure Index, and Analytical Greenness metric.