National Environmental Methods Index Research Articles

Environmentally safe chemometric evaluation and data analysis for the kinetic investigation of mirabegron stability

The physicochemical characteristics of different pharmaceuticals may change with transportation, storage, and usage which directly affect their efficacy, quality, and other features. It is crucial to investigate the kinetic action of pharmaceutical compounds to produce predictive data that aid in the computation of their shelf lives. Several conventional analytical methods introduce unwanted dangerous risks, like employing unsafe solvents, that harm both the analyst and the environment. This created the motive for analysts to apply green approaches that consider using safe chemicals and producing as little waste as possible. In this study, powerful green assessment methods were investigated to study the kinetic process of Mirabegron (MIR) in different hydrolytic conditions giving its main degradation product. First, the optimal solvent was identified for the given kinetic procedures with the aid of Principal Component Analysis. Then two advanced chemometric methods were applied to estimate the kinetic parameters of the MIR degradation process namely: Multivariate Curve Resolution-Alternating Least Squares and Artificial Neural Networks. By data manipulation, both algorithms could provide an explanation of the MIR kinetic process in different hydrolytic conditions. Moreover, modified National Environmental Methods Index (NEMI), eco-scale, Hexagon algorithm, Complementary Green Analytical Procedure Index (Complex GAPI), and analytical greenness metric for sample preparation (AGREEprep) were adopted to ensure the greenness of the proposed study. Eventually, the presented investigation could successfully present an eco-friendly chemometric approach for monitoring the different kinetic processes of pharmaceutical compounds with minimum effort and solvent consumption and maximum time saving and analyst safety compared to other traditional methods.

Simultaneous measurement of duloxetine hydrochloride and avanafil at dual-wavelength using novel ecologically friendly TLC-densitometric method: application to synthetic mixture and spiked human plasma with evaluation of greenness and blueness

The simultaneous assay of duloxetine hydrochloride (DLX) and avanafil (AVN) in their pure forms, synthetic mixtures, and spiked human plasma was achieved using a novel, eco-friendly, sensitive, and specific HPTLC methodology that have been established and validated. Measuring the levels of co-administered antidepressants and sexual stimulants in biological fluids is an important step for individuals with depression and sexual problems. Separation was performed successfully using pre-coated silica gel 60-F254 as a stationary phase and a mobile phase composed of methanol, acetone, and 33% ammonia (8:2:0.05, v/v/v). Compact bands were produced by the optimized mobile phase that was chosen for development (Rf values were 0.23 and 0.75 for DLX and AVN, individually) after dual-wavelength detection for DLX and AVN at 232 and 253 nm, respectively. The results of polynomial regression analysis were exceptional (r = 0.9999 for both medicines) over concentration ranges of 5-800 and 10-800ng/spot for DLX and AVN, respectively. The quantitation limits were 4.69 and 9.53 ng/spot (0.31 and 0.94 µg/mL), whereas the detection limits were 1.55 and 3.15 ng/spot (0.63 and 1.91 µg/mL), for DLX and AVN, respectively. The International Council for Harmonization (ICH) criteria served as the basis for validating the established approach. Moreover, the proposed technique was evaluated in terms of greenness using four contemporary ecological metrics: The Analytical Greenness software (AGREE), the Green Analytical Procedure Index (GAPI), Eco-Scale, and the National Environmental Method Index (NEMI). Additionally, the Blue Applicability Grade Index (BAGI), a newly developed tool for evaluating the practicality (blueness) of procedures, was taken into consideration when evaluating the sustainability levels of the established approach.

Evaluation of the on–off fluorescence method for facile measurement of vilazodone in pharmaceutical dosage form; Application to content uniformity testing and greenness evaluation

Vilazodone is a recently approved antidepressant medicine used for treating major depressive disorder. A simple, extremely sensitive, accurate and green spectrofluorimetric method was constructed for its determination through formation of ion-pair complex with erythrosine B. The formation of ion-pair complex lowers the dye’s native fluorescence emission measured at 552 nm (λ ex = 530 nm). In terms of analysis, the system’s parameters for producing the vilazodone-erythrosine B complex have been optimized. The reaction was carried out through using Teorell-Stenhagen buffering solution (pH 4.6). The fluorescence emission intensity of the dye decreased linearly in the range of 20 – 600 ng mL−1 and the correlation coefficient was 0.9999. The quantitation and detection limit values were 18.5 and 6.1 ng mL−1, respectively. The proposed strategy has been validated according to the ICH criteria. The proposed technique was thoroughly employed for evaluating vilazodone in raw material and pharmaceutical tablet dosage form. Furthermore, it was also successfully used for content uniformity testing. Lastly, using four advanced 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 greenness of the established technique was evaluated.

Rapid synergistic cloud point extraction based on hydrophobic deep eutectic solvent combined with hydride generation atomic absorption spectrometry for determination of selenium in tea samples

Herein, hydrophobic deep eutectic solvents (HDESs) were created for the fast preconcentration of Se(IV) from tea samples at room temperature. A facile and rapid synergistic cloud point extraction (HDES-RS-CPE) procedure was used, followed by hydride generation atomic absorption spectrometry (HG-AAS). The selected synergistic DES included glycine and lauric acid (molar ratio 3:1). 2-hydroxy-5-p-tolylazobenzaldehyde (HTAB) and Triton X-114 were utilized as chelating reagent and non-ionic surfactant, respectively. The experimental parameters that impact extraction recovery were examined and optimized. The detection limit, quantification limit, preconcentration factor, and enhancement factor for Se(IV) under optimum circumstances were 0.02 μg L−1, 0.06 μg L−1, 125, and 149, respectively. The method exhibited analytical linearity in the range up to 700.0 μg L−1. The procedure was used effectively for the quantification of Se(IV) in tea and certified samples. Moreover, the National Environmental Method Index (NEMI), the analytical greenness scale for sample preparation (AGREEprep), and the Green Analytical Procedure Index (GAPI) criteria have been used to measure the greenness score of the extraction procedure. To further highlight the environmental friendliness of this method, a detailed evaluation has been performed.

Simultaneous determination of lesinurad and febuxostat in commercial fixed-dose combinations using a greener normal-phase HPTLC method

Abstract So far, no documented method for simultaneously analyzing lesinurad (LND) and febuxostat (FBX) has been reported for either traditional high-performance thin-layer chromatography (HPTLC) or a green HPTLC technique. In order to determine LND and FBX simultaneously in commercially available fixed-dose combo tablets, this study devised a normal-phase HPTLC method that is fast, sensitive, and green. The green eluents for the simultaneous analysis of LND and FBX were a mixture of ethyl acetate:ethanol:water at 70:20:10 (v/v/v) ratio. The new approach’s greenness was predicted utilizing four distinct greenness tools: the National Environmental Method Index, Analytical Eco-Scale, ChlorTox, and Analytical GREENness approaches, and the results revealed a significantly greener profile. The current method operated on a linear scale between 30 and 1,000 ng·band−1. It was confirmed that the current approach is sensitive, accurate, precise, robust, and green. The LND and FBX contents of commercially available tablet products A and B were found to be within the range of 100 ± 2%, indicating that the existing methodology for simultaneously determining LND and FBX in pharmaceutical combination products is applicable. The results of the current methodology indicated that LND and FBX could be consistently measured in pharmaceutical combination products simultaneously using the current approach.

Determination of 9 fentanyl drugs in environmental water by UHPLC-MS/MS combined with solid phase extraction

In this study, sensitive and selective SPE-UHPLC-MS/MS methods were established and applied to the determination of 9 fentanyl drugs in environmental water, in order to address the lack of research on wastewater-based epidemiology for fentanyl drugs. The methods involved purifying and enriching water samples using homemade PS/DVB-WCX SPE cartridges, followed by UHPLC-MS/MS analysis. In subsequent research, the performance of four SPE cartridges were compared, and the results revealed the superior performance of PS/DVB-WCX in terms of extraction efficiency and matrix removal. Optimized instrument parameters enabled qualitative and quantitative analysis of the 9 fentanyl drugs. For different matrices, two quantitative methods were developed and their correlation coefficient (r2) were all greater than 0.9945. The LODs and LOQs of all analytes were 0.17 ng/L and 0.50 ng/L respectively. Accuracy assessment via spiking standards into environmental water samples showed recoveries ranging from 81.4 % to 109.4 % and 81.6 % to 116.7 % respectively for two methods. The results suggested that the proposed methods were able to meet the needs of 9 fentanyl drugs monitoring in environmental water. Additionally, the greenness assessment of the proposed analytical method was evaluated by three greenness assessment metrics: National environmental methods Index (NEMI), Green analytical procedure Index (GAPI), and Analytical GREEnness metric (AGREE). The results indicate that the established method is environmentally friendly.

A Green HPLC Approach to Florfenicol Analysis in Pig Urine.

Florfenicol (FF) is a broad-spectrum antibiotic used to treat gastrointestinal and respiratory infections in domestic animals. Considering FF's rapid elimination via urine after drug treatment, its use increases concerns about environmental contamination. The objective of the study was to establish a sustainable chromatographic method for simple analysis of FF in pig urine to investigate the urinary excretion of FF after a single intramuscular administration of 20 mg FF/kg body weight. The urine sample was prepared using a centrifuge and regenerated cellulose filter, and the diluted sample was analyzed. The method was validated in terms of linearity, the limit of detection (0.005 µg/mL) and quantitation (0.016 µg/mL), repeatability and matrix effect (%RSD ranged up to 2.5), accuracy (varied between 98% and 102%), and stability. The concentration-time profile of pig urine samples collected within 48 h post-drug administration showed that 63% of FF's dose was excreted. The developed method and previously published methods used to qualify FF in the urine of animal origin were evaluated by the National Environmental Method Index (NEMI), Green Analytical Procedure Index (GAPI) and Analytical GREENness Metric Approach (AGREE). The greenness profiles of published methods revealed problems with high solvents and energy consumption, while the established method was shown to be more environmentally friendly.

EVALUATION OF GREENNESS PROFILES OF VARIOUS DEVELOPED METHODS FOR THE DETERMINATION OF COMMONLY USED NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs) IN ENVIRONMENTAL WATERS

Objective: In our study, it was aimed to make a comparative analysis of the environmental impact profiles of two approaches including Gas Chromatography (GC) and Liquid Chromatography (LC) methods, which are frequently used techniques for the determination of non-steroidal anti-inflammatory drugs (NSAIDs) and their metabolites in environmental water samples. Material and Method: The evaluation of the methods' environmental impact was performed using National Environmental Methods Index Label (NEMI), Analytical Eco-scale, Analytical GREEnness Metric (AGREE), and Green Analytical Procedure Index (GAPI). Result and Discussion: The routine analysis of NSAIDs in environmental waters is carried out, resulting in a significant volume of chemical waste. In recent times, there has been a growing significance attributed to environmentally conscious analytical methodologies and the evaluation of methodologies through a green lens to confront this challenge. There is no statistically significant difference in terms of environmental impact profile was observed between the two methods compared.

Greenness-sustainability metrics for assessment smart-chemometric spectrophotometric strategy for evaluation of the combination of six gastric proton-pump inhibitors with two selected impurities

Green analytical approaches are employed for the determination of active pharmaceutical ingredients, in conjunction with their impurities. Smart chemometric spectrophotometric techniques, including orthogonal partial least square (OPLS), variable selection such as genetic algorithm (GA-OPLS), and interval selection (i-OPLS), were utilized. These chemometric models were implemented for assessing six proton-pump inhibitors Omeprazole, Esomeprazole, Lansoprazole, Pantoprazole, Rabeprazole, and Dexlansoprazole along with two selected official impurities, namely 4-Desmethoxy omeprazole impurity and Rabeprazole-impurity B. Experimental design was implemented to separate impurities, in the process of multivariate calibration, a five-level eight-factor calibration design consisting of 25 samples was selected. This design was deliberately selected to guarantee that the components were mutually orthogonal to assess the model's performance and reliability, a separate validation set of 15 samples was constructed. The best-performing of the proposed techniques were identified by considering the least favorable values of the Correlation Coefficient (R ≥ 0.9995), the Root Mean Square Error of Prediction (RMSEP) values between (0.0102–0.5622), and the Relative Error of Prediction (REP) values between (0.2961–1.1917). The proposed and reported methods' greenness-sustainability was quantitatively evaluated, and a comparative study of the greenness profile was established through a spider chart, the National Environmental Method Index tool, advanced and modified NEMI along with the Hexagon tool, and the whiteness qualities of the presented approaches were assessed by implementing the recently adopted Red-Green-Blue paradigm and White Analytical Chemistry tool. These approaches are well-suited for use in quality control laboratories due to their observed acceptance, long-term sustainability, simplicity, and affordability.

Four chemometric models enhanced by Latin hypercube sampling design for quantification of anti-COVID drugs: sustainability profiling through multiple greenness, carbon footprint, blueness, and whiteness metrics

Montelukast sodium (MLK) and Levocetirizine dihydrochloride (LCZ) are widely prescribed medications with promising therapeutic potential against COVID-19. However, existing analytical methods for their quantification are unsustainable, relying on toxic solvents and expensive instrumentation. Herein, we pioneer a green, cost-effective chemometrics approach for MLK and LCZ analysis using UV spectroscopy and intelligent multivariate calibration. Following a multilevel multifactor experimental design, UV spectral data was acquired for 25 synthetic mixtures and modeled via classical least squares (CLS), principal component regression (PCR), partial least squares (PLS), and genetic algorithm-PLS (GA-PLS) techniques. Latin hypercube sampling (LHS) strategically constructed an optimal validation set of 13 mixtures for unbiased predictive performance assessment. Following optimization of the models regarding latent variables (LVs) and wavelength region, the optimum root mean square error of cross-validation (RMSECV) was attained at 2 LVs for the 210–400 nm spectral range (191 data points). The GA-PLS model demonstrated superb accuracy, with recovery percentages (R%) from 98 to 102% for both analytes, and root mean square error of calibration (RMSEC) and prediction (RMSEP) of (0.0943, 0.1872) and (0.1926, 0.1779) for MLK and LCZ, respectively, as well bias-corrected mean square error of prediction (BCMSEP) of -0.0029 and 0.0176, relative root mean square error of prediction (RRMSEP) reaching 0.7516 and 0.6585, and limits of detection (LOD) reaching 0.0813 and 0.2273 for MLK and LCZ respectively. Practical pharmaceutical sample analysis was successfully confirmed via standard additions. We further conducted pioneering multidimensional sustainability evaluations using state-of-the-art greenness, blueness, and whiteness tools. The method demonstrated favorable environmental metrics across all assessment tools. The obtained Green National Environmental Method Index (NEMI), and Complementary Green Analytical Procedure Index (ComplexGAPI) quadrants affirmed green analytical principles. Additionally, the method had a high Analytical Greenness Metric (AGREE) score (0.90) and a low carbon footprint (0.021), indicating environmental friendliness. We also applied blueness and whiteness assessments using the high Blue Applicability Grade Index (BAGI) and Red–Green–Blue 12 (RGB 12) algorithms. The high BAGI (90) and RGB 12 (90.8) scores confirmed the method's strong applicability, cost-effectiveness, and sustainability. This work puts forward an optimal, economically viable green chemistry paradigm for pharmaceutical quality control aligned with sustainable development goals.

Utility of sustainable ratio derivative spectrophotometry for the concurrent assay of synergistic repurposed drugs for COVID-19 infections; Insilico pharmacokinetics proof

The cutting-edge combination of fluvoxamine (FVM) and ivermectin (IVM) has been presented as a proposed dosage form for the treatment of COVID-19 infections in early diagnosed patients. The main objective of this work is to develop simple, sensitive, and efficient methods for the synchronous quantification of FVM and IVM without any prior separation. Four green UV-methods were employed for the synchronous quantification, namely: Fourier functions convolution of absorption spectra, FFAS, Fourier functions convolution of derivative spectra of absorption curves, FFDS, Fourier function convolution of ratio spectra of absorption curves, FFRS and the dual-wavelength method, DWM. FFRS and DWM approaches can be able to reconcile the two components' significantly interfering spectrum presented in this commixture. Good linearity was checked in the range of 5–40, and 2.5–25 μg/mL for the FVM, and IVM, respectively. All approaches developed have been recommended in compliance with ICH principles. Furthermore, the approaches’ greenness was predestined by “National Environmental Method Index” (NEMI), “Analytical GREEnness metric (AGREE)”, the “Analytical Eco-Scale”, and the “Green Analytical Procedure Index” (GAPI). In addition, spider diagram was utilized for the assessment of the greenness index of the solvent used. Beside greenness, the sustainability of our methods was investigated using the HEXAGON tool. Continuing the constant pursuit of greenness, drug-drug interactions (DDIs) between FVM & IVM were predicted by insilico tools to ensure the safety of the suggested mixture as a preliminary step before invitro and in vivo studies. Because they were deemed sustainable, affordable, and successful, the suggested UV-methods may be used for routine quality control investigations of the indicated formulations FVM & IVM.

A comparative analysis of univariate versus multivariate eco-friendly spectrophotometric manipulations for resolving severely overlapped spectra of vonoprazan and amoxicillin new combination

Vonoprazan and amoxicillin are pharmacological combinations that demonstrate synergistic effects in treating Helicobacter pylori (H. pylori), a global public health concern associated with peptic ulcer disease and gastric cancer. Four spectrophotometric methods were developed, including two univariate techniques (Fourier self-deconvolution and ratio difference) and two multivariate chemometric approaches (partial least squares and principal component regression). These methods provide innovative solutions for effectively resolving and accurately quantifying the overlapping spectra of vonoprazan and amoxicillin. The concentration ranges covered were 3–60 μg ml−1 for vonoprazan and 5–140 μg ml−1 for amoxicillin. To assess the environmental sustainability of the methodologies, various measures such as the Green Analytical Procedure Index (GAPI), National Environmental Method Index (NEMI), Analytical GREEnness Calculator, and Analytical Eco-scale, as well as RGB12 and hexagon toll were implemented. The validation of the developed techniques was carried out in compliance with ICH standards. The present study is highly significant because it is the first time that the mixture has been determined using the current approaches. The comparative analysis demonstrated no significant difference in terms of accuracy and precision compared to reference HPLC method (p = 0.05). The established spectrophotometric methods offer a straightforward, rapid, and cost-effective alternative to complex analytical techniques for determining the vonoprazan and amoxicillin mixture. They show potential for routine analysis in research laboratories and pharmaceutical industries.

Two green and sensitive spectrofluorimetric approaches for determination of Ambroxol and guaifenesin in their single and combined pharmaceutical formulations.

Ambroxol hydrochloride (AMX) and guaifenesin (GFN) are approved drugs utilized to treat coughs through their potent mucolytic and expectorant properties. Due to their massive, combined administration in many illnesses, there is a persistent need for their concurrent estimation in different pharmaceutical formulations. Two sensitive, environmentally friendly spectrofluorimetric methods were developed. AMX was determined using the first method (I) without interference from GFN. This method depends on the quenching of Erythrosine B (EB) native fluorescence at 552 nm after excitation at 527 nm due to the formation of a non-fluorescent AMX-EB ion-pair complex in Britton-Robinson buffer (BRB) solution pH (3.5). The concentration plot is linear over the 0.25-5.0μg/mL range, with a mean percent found value of 99.74%. Method (II) depends on measuring the native fluorescence of aqueous GFN solution at two analytical wavelengths, either 300 or 600 nm, after excitation at 274 nm. Relative fluorescence intensity (RFI)-concentration plots are linear over the ranges of 0.02-0.5 and 0.1-2.0μg/ml, with mean percent found at 99.96% and 99.91% at dual wavelengths, respectively. The proposed methods were successfully applied to assay both drugs in raw materials and different single and combined pharmaceutical formulations. These methods have been thoroughly validated following International Committee on Harmonisation (ICH) guidelines. National Environmental Methods Index, Analytical Eco-Scale, and Green Analytical Procedure Index were used to prove greenness, thereby enhancing their applicability. The proposed techniques provide straightforward, precise, and cost-effective solutions for routine formulation analysis in quality control laboratories.

Simultaneous estimation of ibuprofen, caffeine, and paracetamol in commercial products using a green reverse-phase HPTLC method

Abstract A fast, sensitive, and green reverse-phase “high-performance thin-layer chromatography” approach for the simultaneous estimation of ibuprofen (IBF), caffeine (CAF), and paracetamol (PCM) in marketed formulations was established and verified in this study. The binary combination of acetone and water (80:20 v/v) was used as the green eluent system. The current method’s greenness was predicted using four different approaches, namely National Environmental Method Index, Analytical Eco-Score (89), ChlorTox (1.08 g), and the Analytical GREENness (83) approaches, which demonstrated an outstanding greener profile. The present approach was linear in the range of 25–800 ng·band−1 for the simultaneous estimation of IBF, CAF, and PCM. In addition, the current method was accurate (% recoveries = 100 ± 2), precise (%CV < 2%), robust (%CV < 2), sensitive (LOD = 1.13–2.71 ng·band−1 and LOQ = 3.39–8.10 ng·band−1), and green. The amount of IBF, CAF, and PCM in commercial tablets was determined to be 99.51%, 98.25%, and 100.64%, respectively. The present method for the simultaneous determination of IBF, CAF, and PCM in marketed tablets is supported by these data. The findings of this study suggested that the current approach may be consistently applied to analyze IBF, CAF, and PCM in marketed tablets.

A comprehensive exploration of diverse green analytical techniques and their influence in different analytical fields

AbstractThe primary goals of green analytical chemistry (GAC) involve the development of novel analytical technologies or the modification of existing methods to incorporate procedures with reduced reliance on hazardous chemicals. Several approaches can be employed to achieve these objectives, including the utilization of environmentally friendly solvents and reagents, shortening chromatographic separation times, and the miniaturization of analytical devices. The review summarizes the evolution of GAC with its specific principles and with special emphasis on recent applications in modern era. A detailed exploration of the choice of green solvents and their practical utilization in green liquid chromatography (LC) techniques for environmentally friendly analysis of pharmaceuticals has been discussed. An ordinary description with a tabular illustration of various modern green analytical techniques like micellar LC, superheated water chromatography, high‐speed LC, enhanced fluidity LC, two‐dimensional LC, and aspects of gas chromatography has been thoroughly provided for concepts with their mechanism and limitations. GAC provides potential applications for food analysis, environmental analysis of pharmaceutically active compounds in the aquatic environment with special emphasis on strategies for greening LC and impurity profiling, and so on. Numerous benefits, limitations, and challenges that are linked to the field of GAC are highlighted in this review. We pay special attention to new green approaches, such as automation, miniaturization, direct analysis techniques, and some initiatives like the National Environmental Methods Index Label for Analytical Eco‐Scale assessment. In spite of many promising advancements, the understanding is still limited and challenging.

Greenness, whiteness, and blueness assessment with spider chart solvents evaluation of HPTLC-densitometric method for quantifying a triple combination anti-Helicobacter pylori therapy

Tackling environmental, economic, and practical issues necessitate analytical methods aligned with green and white chemistry principles. This study quantified a challenging combination of three anti-Helicobacter pylori drugs: omeprazole (OMZ), tinidazole (TNZ), and clarithromycin (CLR) using a novel high-performance thin-layer chromatographic approach. The eco-friendly mobile phase comprised a mixture of ethyl acetate and ethanol (6.5:3.5, v/v), with densitometric detection at 290 nm, yielding compact spots for OMZ (Rf 0.27), TNZ (Rf 0.63), and CLR (Rf 0.73). The method demonstrated excellent linearity (r2 > 0.999) over ranges of 0.5–20, 1–50, and 1–25 μg spot−1 for OMZ, TNZ, and CLR, respectively. Method validation showed good precision (<2 %), accuracy (101.94, 100.65, 101.06 %), and the limit of detections (0.161, 0.269, and 0.283 μg spot-1), for OMZ, TNZ, and CLR, respectively. To ensure sustainability, hazardous solvents were replaced with greener alternatives selected using the Green Solvents Selecting Tool and assessed via greenness index spider charts. The greenness evaluation of the developed method achieved a greener National Environmental Method Index (NEMI), and Complementary Green Analytical Procedure Index (ComplexGAPI) quadrants with higher Analytical Greenness Metric (AGREE) (0.81) and lower carbon footprint (0.037) revealing the method's favorable environmental profile. We further applied the concepts of 'blueness' and 'whiteness' assessment using the recently introduced Blue Applicability Grade Index (BAGI) and Red-Green-Blue 12 (RGB 12) algorithms. The high BAGI score (90) indicated excellent applicability, while the RGB12 score (88.9) confirmed cost-effectiveness and sustainability. This novel HPTLC approach offers a rapid, green-and-white alternative to conventional techniques for pharmaceutical analysis.

Eco-friendly liquid chromatography method for the quantification of ibrutinib in a pharmaceutical dosage form.

The objective of this study was to quantitatively determine Bruton's tyrosine kinase inhibitor ibrutinib in its capsule dosage form and assess the homogeneity of the dosage form using green chromatography. The chromatographic method using gradient elution mode was optimized and validated in accordance with the International Council for Harmonization guidelines. The analysis was conducted on a Zodiac C18 column (75 × 4.6 mm and 3.5 μm) using a mobile phase consisting of pH 5.5 potassium phosphate buffer (mobile phase A) and 90% ethanol in milli-Q water (mobile phase B), with a flow rate set at 0.6 mL/min. Based on the validation data, the accuracy results fell within the range of 99.1%-100.6%. The relative standard deviation (% RSD) from precision for both the assays and the uniformity of dosage by content uniformity were determined to be 0.82 and 1.16, respectively. The correlation coefficient obtained from the linearity experiment was 0.999, indicating a strong linear relationship. The greenness of the developed method was assessed using various tools, including the National Environmental Methods Index (NEMI) pictogram, Modified NEMI, Analytical Eco-score calculation, Green Analytical Procedure Index (GAPI) pictogram, Analytical GREEnness (AGREE), and AGREE preparation (AGREEprep). The obtained greenness profile suggests that the optimized LC method is an excellent greener method, supported by the analytical eco-score of 86.

An innovative combination of Box-Behnken design and ecofriendly approaches for the simultaneous determination of aspirin, clopidogrel, atorvastatin and rosuvastatin in their fixed-dose combination tablets

Three-levels Box-Behnken design was used in the experimental design approach for the optimization of chromatographic parameters to achieve the optimum resolution and sharp peak shape within a reasonable run time. A method that is sensitive, reliable, and selective was constructed and validated for the simultaneous measurement of a combination therapy that contains blood-thinning and cholesterol-lowering compounds. The four cited drugs namely, aspirin (ASP), clopidogrel (CLP), atorvastatin (ATV) and rosuvastatin (ROS) were estimated in bulk and in pharmaceutical dosage forms in line with International Council for Harmonization guidelines. The separation was done utilizing Kinetex 2.6 C18 column (100 mm, 4.6 mm, 5 m) and RP-HPLC with diode array detector. The separation of the cited drugs and the degradation product of ASP was achieved with mobile phase composed of acetonitrile: KH2PO4 buffer in a gradient mode with pH 3.2 at room temperature. The four drugs were linear over the concentration range (0.05–50 µg/mL). The technique is feasible to be used in quality control laboratories. To picture the green profile of the developed method, four greenness assessment tools were applied. National environmental methods index (NEMI), analytical eco-scale assessment (ESA), green analytical procedure index (GAPI) and analytical greenness metric (AGREE) are the most widely used metrics. They were employed to evaluate the greenness profile of the proposed method and to perform a detailed greenness comparison between the developed method and some of the reported methods for the determination of the investigated drugs. The developed method was found to be relatively green with 0.54 AGREE score.

Greenness assessment of two chromatographic methods developed for the determination of Mupirocin in two binary mixtures along with its impurity

Two simple, accurate and precise chromatographic methods have been developed and validated for estimating Mupirocin (MUP) in two binary mixtures. Mixture (1); with Fluticasone propionate (FLU) together with two of their impurities, namely; Pseudomonic acid-D (Pseud-D) and Fluticasone impurity C (FIC). Mixture (2); with Mometasone furoate (MF) along with Pseud-D impurity. High performance thin layer chromatography (HPTLC-densitometry) and high performance liquid chromatography (RP-HPLC) were the two proposed methods. In the HPTLC method, good separation of both mixtures was achieved by using HPTLC plates pre-coated with silica gel 60 F254 as stationary phase and the mobile phase consisted of toluene: chloroform: ethanol at a ratio of (5: 4: 2, by volume). The detection was carried out at 220 nm for MUP and 254 nm for FLU, MF, Pseud-D and FIC. In the HPLC method, chromatographic separation was carried out using Agilent Eclipse XDB (250 mm×4.6 mm, 5 μm) C18 column. For mixture (1), a mobile phase of methanol: sodium di-hydrogen phosphate (pH 3.0) was applied in stepwise gradient elution starting at ratios of (50: 50, v/v) and then switching to (80: 20, v/v) after 7 min at a flow rate of 1 mL.min− 1. Detection was performed using diode array detector at 220 nm for MUP and Pseud-D and 240 nm for FLU and FIC. For mixture (2), the same mobile phase was used, but in isocratic elution in the ratio (80: 20, v/v) at flow rate of 1 mL.min− 1 and detection at 220 nm for MUP and Pseud-D and 248 nm for MF. The two methods successfully separated the cited drugs and were used to determine the drugs in pure form as well as pharmaceutical dosage forms. Validation was done as per International Council on Harmonization guidelines. Furthermore, the greenness of the proposed methods compared to the reported method, was evaluated as per the National Environmental Method Index, analytical Eco scale, Green Analytical Procedure Index and Analytical Greenness metric approaches.

Green analytical profiling of Teucrium chamaedrys L. using natural deep eutectic solvents and planar chromatography: a greenness assessment by the National Environmental Methods Index and analytical eco-scale

Green analytical profiling of Teucrium chamaedrys L. using natural deep eutectic solvents and planar chromatography: a greenness assessment by the National Environmental Methods Index and analytical eco-scale