Eco-scale Assessment Research Articles

Development of a novel chromatographic method for concurrent determination of 5-fluorouracil and cisplatin: Validation, greenness evaluation, and application on drug-eluting film

The combination of 5-fluorouracil (5-FU) and cisplatin (Cis) has been used for the treatment of many cancers. The combination demonstrates synergy and improved clinical outcomes encouraging developing a formulation with both drugs. An analytical procedure is essential for formulation studies; however, no method has been reported for the concurrent determination and quantification of both 5-FU and Cis to date. A novel, simple, accurate, and precise HPLC method was developed using a C18 column (250 mm × 4.6 mm, 5 µm) and mobile phase composed of 0.5 mM sodium dodecyl sulfate: methanol (98:2, v/v), adjusted to pH 2.5 with phosphoric acid. A flow rate of 0.5 mL/min was applied and a photodiode array was utilized for detection and the retention times were 9.89 min (265 nm) for 5-FU and 5.36 min (210 nm) for Cis. Validation procedures were performed, and the method was found to be linear at ranges of 0.9–60.0 µg/mL for 5-FU and 6.0–60.0 µg/mL for Cis. The limits of detection (LOD) and quantitation (LOQ) were 0.10 and 0.25 µg/mL for 5-FU and 2.00 and 4.00 µg/mL for Cis, respectively. Other parameters such as precision, selectivity, robustness, and stability results were within acceptable limits. The method was applied to a model co-eluting film and its release profile was studied. Additionally, the method’s greenness was evaluated by four assessment tools namely the national environmental method index (NEMI), analytical eco scale assessment (ESA), green analytical procedure index (GAPI), and Analytical GREEnness Metric Approach and Software (AGREE). The results demonstrated compliance with green analytical chemistry (GAC) practices. This research acts as a step towards further investigation of drug stability under different stress conditions and quantification of the intact drugs in presence of their degradation products.

Green and Cost-Effective Extraction Techniques of Quercetin from Mixture of Nutraceuticals with Yield Analysis via Spectrophotometry and High-Performance Liquid Chromatography Methods.

Extraction is the leading critical stage in the analysis of nutraceuticals. Ginkgo biloba (GB) has gained interest because of its therapeutic usages. The aim was to develop four cost-effective extraction techniques for the extraction of quercetin from GB in a sachet containing a mixture of nutraceuticals. These techniques are solid-phase extraction (SPE), liquid-liquid extraction, inverted dispersive liquid-liquid microextraction, and the QuEChERS (quick, easy, cheap, effective, rugged, and safe) method. Direct spectrophotometry was used to monitor the recovery of the standard quercetin throughout the optimization steps. The HPLC-UV method of analysis was optimized to quantify the yields from the extracts present in the complicated contents of the sachets. The present study was assessed by analytical Eco-Scale assessment (ESA) and the National Environmental Method Index (NEMI) for greenness in comparison with the literature. SPE showed the best cleanup outcomes. ESA and NEMI showed an adequate greenness of the proposed extraction protocol. Quercetin (marker for GB) extraction from market nutraceutical sachets is considered an exemplar for analysis in the QC of nutraceuticals. Regarding the greenness results, the proposed method of extraction is better even with adequate greenness as the extraction was a one-step process, in comparison with multistep processes of previously published protocols. Accordingly, it is recommended for use in routine extraction and analysis of such nutraceuticals. Four extraction protocols have been developed. For GB ternary-mixture sachets, proper recovery was obtained using C18 SPE. The assessment of greenness of the proposed protocol guaranteed the superiority of the presented method. Safer sorbents and chemicals are favored for use in routine extraction of nutraceuticals.

Ecologically evaluated and FDA-validated HPTLC method for assay of pregabalin and tramadol in human biological fluids.

The introduced research presents a novel in vivo quantitative method for assay of mixtures of pregabalin and tramadol as a common combinations approved for treatment of neuropathic pain. Green analytical chemistry is a recently emerging science concerned with control of the use of chemicals harmful to the environment in various analytical methods. Consequently, a green high-performance thin layer chromatography (HPTLC) method was achieved for determination of the mixture in human plasma and urine satisfying both analytical and environmental standards. The separation was achieved on HPTLC sheets using a separating mixture of ethanol-ethyl acetate-acetone-ammonia solution (8:2:1:0.05, by volume) as a mobile phase. The sheets were dried in air then scanned at two wavelengths. For tramadol, 220 nm was chosen; however, pregabalin is an unconjugated drug, so its determination was a challenge. Hence for pregabalin, the plates were sprayed with ethanolic solution of ninhydrin (3%, w/v), to obtain a conjugated complex, which could be assessed at 550 nm. Furthermore, the developed method fulfilled the US Food and Drug Administration validation guidelines, and proved to be useful in therapeutic drug monitoring of this combination. The Eco-scale assessment protocol was implemented to determine the greenness profile of the applied method.

US FDA-validated green GC-MS method for analysis of gabapentin, tramadol and/or amitriptyline mixtures in biological fluids.

Background: Mixtures of gabapentin, tramadol and/or amitriptyline are usually recommended for treatment of neuropathic pain. Materials & methods/results: A novel GC-MS/MS method was developed to assess the studied mixture whether in pure forms or human biological fluids (plasma/urine). The chromatographic detection was performed using MS detector applying the selected ion-monitoring mode. An (Agilent, CA, USA)GC-MS with triple axis single quadrupole detector unit was used for the analysis equipped with HP-5MS (5% phenyl methyl siloxane) column. Helium was the carrier gas and positive electron impact ionization mode was applied. Conclusion: The developed method was able to assess the mixture components simultaneously within six minutes. Validation of the method was assured according to USFDA guidelines and Eco-Scale assessment.

Validation and eco-scale assessment of stability-indicating HPTLC method for quantitative analysis of carbamazepine and its degradation product, iminostilbene, in pure forms, pharmaceutical preparations, and spiked human plasma

Paying attention to issue of environmental protection is an unavoidable duty which encourages analytical society to balance between establishment of new analytical method and preservation of the environment from the harmful chemicals. By adopting this concept, an excellent green high-performance thin-layer chromatography (HPTLC) method was developed for assessment of carbamazepine, the antiepileptic drug, and iminostilbene, the main degradation product and its official impurity. Separation of the structurally related components was completed on HPTLC sheets using a mixture of petroleum ether: acetone (7:3, v/v) as a developing system with UV detection at 230 nm. To assess the greenness profile of the developed method compared with the official high-performance liquid chromatography (HPLC) method, analytical semi-quantitative eco-scale assessment protocol was applied. The suggested method was confirmed to be greener than the official method with regard to solvent consumption and waste emission. The suggested method was successfully applied to determine carbamazepine in the marketed dosage forms with no intrusion of other co-formulated ingredients. Successful application of the developed method was also proved via simultaneous analysis of carbamazepine and iminostilbene in raw materials and human plasma samples in ranges of 0.1–1.4 μg/band and 0.1–1.2 μg/band for carbamazepine and iminostilbene, respectively. As the maximum plasma concentration of the studied medication was within its calibration range, the proposed HPTLC method can be employed for further pharmacokinetic studies. For comprehensive validation of the presented method, ICH figures of merit were evaluated.

Impurity profiling high-performance-thin-layer chromatography method involving the assay of essential human micronutrient niacin with eco-scale assessment.

Currently, analytical scientists are paying special attention to reducing reliance on hazardous chemicals in various analytical methods. By embracing this concept, we developed an eco-friendly high-performancethin-layer chromatography (HPTLC) method as an alternative for the conventional HPLC method for the determination of an essential human micronutrient, niacin (NIA), which is used improve the lipid profile of patients. Furthermore, the proposed HPTLC method is capable of determining the structurally related impurities of NIA such as pyridine-2,5-dicarboxylic acid, isonicotinic acid, pyridine, and 5-ethyl-2-methylpyridine, which exhibit nephrotoxic and hepatotoxic effects. The separation of this challenging mixture was achieved on HPTLC sheets using a mixture of ethyl acetate/ethanol/ammonia solution (6:4:0.05, v/v/v), and then the dried plates were scanned at 254 nm. The analytical eco-scale assessment protocol was used to assess the greenness profile of the presented method and compare it with the reported HPLC method. The suggested method was found to be greener with regard to the consumption of solvents and the yielding of waste. The results suggest that the described method can be safely implemented for the routine analysis of NIA pharmaceutical dosage without the interference of potential impurities in quality control laboratories.

Sustainable Eco-Friendly Ultra-High-Performance Liquid Chromatographic Method for Simultaneous Determination of Caffeine and Theobromine in Commercial Teas: Evaluation of Greenness Profile Using NEMI and Eco-Scale Assessment Tools.

Background: Green analytical chemistry (GAC) aims to eliminate or minimize the amount of hazardous solvents consumed and generated daily worldwide. Considering the environmental impact of all analytical procedures and replacing the polluting methodologies with clean ones is of a paramount interest. Objective: This work aims to develop and validate a sustainable, fast, and economic ultrahigh-performance liquid chromatography method for simultaneous determination of methylxanthines in commercial tea samples as well as to evaluate the greenness profile of the proposed method using two greenness assessment tools: National Environmental Methods Index (NEMI) and analytical Eco-scale. Methods: The method was designed based on applying GAC principles in method development. The green chromatography approach was applied by using benign mobile phases. The chromatographic separation was optimized to minimize sample preparation, achieve short analysis time with low solvent consumption, and minimize waste generation. Results: All the studied analytes were separated in only 1.7 min. The detection limits of the studied analytes ranged from 0.015 to 0.03 mg/L, while LOQs were in the range of 0.05 to 0.1 μg/L with UV detection. The proposed method neither uses nor generates harmful chemicals, it passes the four quadrants of the NEMI greenness profile, and it has a high Eco-scale score. Conclusions: Compared with the reported methods, the proposed method is greener, more economical, and faster; therefore, it can be used as a green alternative to the existing conventional methods for routine analysis of the studied analytes without harming the environment.

Development and validation of eco-friendly strategies based on thin film microextraction for water analysis

The aim of the current study is the establishment of Green Analytical Chemistry strategies for water analysis by elimination/reduction of hazardous chemicals, energy consumption, and waste generation throughout the entire analytical workflow. The first approach introduced in this manuscript consists of addition of water to a sampling vessel that contains a thin film microextraction (TFME) device, followed by removal of the device after equilibration, and subsequent quantification of the extracted components by thermal desorption GC/MS. In this approach, namely the in-bottle TFME approach, analyte-loss associated errors that stem from analyte adherence to glass surfaces and/or degradation are avoided as extraction occurs in situ, while analytes are isolated from a complex matrix that contains degradation agents (bacteria, oxidizing or reducing species, etc.). This procedure also circumvents the splitting of original samples into sub-samples. The second approach involves the use of portable TFME devices that facilitate on-site extraction of compounds, therefore eliminating the use of collection vessels, a factor known to potentially introduce errors into analysis. The herein described procedure involves attachment of the TFME device to drill accessories, analyte extraction via direct immersion into sampled site, and subsequent on-site instrumental analysis, which is carried out with the use of a portable GC/MS containing an appropriate thermal desorption interface, or alternatively, by transferring the membrane to the laboratory for bench-top GC/MS analysis. To facilitate a better understanding of the processes governing the developed approaches, modeling by COMSOL Multiphysics® software was performed. The findings of this study were applied for further method optimization, and the optimized developed methods were then applied for on-site surface water analyses. Finally, the greenness of the developed methods was evaluated with use of the eco-scale assessment, with obtained scores compared to that of the US EPA 8270 method.

Development and validation of an eco-friendly SPE-HPLC-MS method for simultaneous determination of selected parabens and bisphenol A in personal care products: Evaluation of the greenness profile of the developed method

Green analytical chemistry (GAC) aims at eliminating the harmful impacts of hazardous chemicals on human health and the environment. Replacing the polluting analytical methodologies with clean ones is of paramount importance. In this study, an eco-friendly fast LC–MS method has been developed for the simultaneous determination of methyl praben, ethyl paraben, propyl paraben, benzyl paraben and bisphenol A in twenty commercial personal care products. GAC principles were applied at all the steps of method development. Sample preparation and clean up was performed with solid-phase extraction on Oasis HLB cartridges and using ethanol as a green eluting solvent. The chromatographic separation was optimized in order to achieve short retention times (6 min) and minimized waste generated (1.8 mL/run) using ethanol as a benign solvent in a gradient elution mode. The method was validated according to International Conference on Harmonization guidelines. Good recoveries were obtained for all analytes ranging from 96% to 103%. The method is robust and all the analytes exhibited high linearity (r2 ≥ 0.998). The greenness profile of the presented method was evaluated using National Environmental Methods Index and analytical Eco-scale assessment tools. The developed method is fast, green, robust and offers benefits both environmentally and economically.

Multicriteria decision analysis in ranking of analytical procedures for aldrin determination in water

The study presents the possibility of multi-criteria decision analysis (MCDA) application when choosing analytical procedures with low environmental impact. A type of MCDA, Preference Ranking Organization Method for Enrichment Evaluations (PROMETHEE), was chosen as versatile tool that meets all the analytical chemists – decision makers requirements. Twenty five analytical procedures for aldrin determination in water samples (as an example) were selected as input alternatives to MCDA analysis. Nine different criteria describing the alternatives were chosen from different groups – metrological, economical and the most importantly – environmental impact. The weights for each criterion were obtained from questionnaires that were sent to experts, giving three different scenarios for MCDA results.The results of analysis show that PROMETHEE is very promising tool to choose the analytical procedure with respect to its greenness. The rankings for all three scenarios placed solid phase microextraction and liquid phase microextraction – based procedures high, while liquid–liquid extraction, solid phase extraction and stir bar sorptive extraction – based procedures were placed low in the ranking. The results show that although some of the experts do not intentionally choose green analytical chemistry procedures, their MCDA choice is in accordance with green chemistry principles. The PROMETHEE ranking results were compared with more widely accepted green analytical chemistry tools – NEMI and Eco-Scale. As PROMETHEE involved more different factors than NEMI, the assessment results were only weakly correlated. Oppositely, the results of Eco-Scale assessment were well-correlated as both methodologies involved similar criteria of assessment.