Green method for quantification of clindamycin in capsules by National Environmental Methods Index, Eco-Scale Assessment and Analytical GREEnness Metric

The use of antiparasitics, such as ivermectin (IVE), is extremely important to public health and economy. Quality control and analytical development are necessary to guarantee the efficacy, safety and quality of medicines. The work covered the development and validation of a green and lean method by UV to quantify IVE in injection solution for veterinary. UV methodology using ethanol as a diluent, quartz cuvette and spectrophotometer at 245 nm were used. In order to bring objectivity in relation to the greenness of the proposed method, 5 tools were used: National Environmental Method Index (NEMI), Eco-Scale Assessment (ESA), Analytical GREEnness Metric (AGREE), Green Analytical Procedure Index (GAPI), Blue Applicability Grade Index (BAGI). The proposed method was linear in the range of 6-16 µg mL-1, precise (RSD < 5%), selective and indicative of stability by forced degradation, exact (100.07%) and robust against small and deliberate modifications. NEMI showed the 4 green quadrants, GAPI showed predominantly green and yellow quadrants, ESA, AGREE and BAGI showed scores of 96, 0.82 and 65, respectively. The method is an excellent and lean green option for evaluating final IVE product. It has an environmentally friendly footprint, which can be advantageously employed by pharmaceutical chemical laboratories worldwide.

More environment-friendly solvents in analytical chemistry are almost inevitable in both sample preparation and analysis to meet the high standards of sustainable chemistry and human welfare. In this review paper, a critical look at the advantages and still unsolved problems of most potential classes of green solvents is presented to give an overview of the current state-of-the-art in this field. Replacing volatile organic compounds (VOCs) by ecofriendly and benign solvents in extractions/separations in sample preparation, as the most tedious and demanding step in analysis, is one of roads toward sustainable chemistry. Water under sub- and supercritical conditions, carbon-dioxide, ionic liquids (ILs), deep eutectic solvents (DESs), and those of natural origin (NADES) belong to the most promising classes of solvents in green analytical chemistry. Basic theory and mechanisms of their use illustrated by representative but not exhaustive list of examples related to complex matrices (environmental and natural food products) from analytical practice are presented in this review. Perspectives of QuEChERS, in line with GAC principles, are highlighted, in line with current trends of "going green" for quick, easy, cheap, effective, rugged, and safe analytical methods. Compliance with green chemistry (GC), especially green analytical chemistry (GAC) principles, is not a fashionable issue but, more the trend toward a sustainable future with greener chemistry; thus, green metrics are an unavoidable tool to measure how green the applied method or procedure is. Herein, the most common tools will be presented and discussed, such as national environmental method index (NEMI), analytical ecoscale, green analytical procedure index (GAPI), analytical greenness calculator (AGREE), complementary green analytical procedure index (ComplexGAPI), and analytical greenness metric for sample preparation (AGREEprep). The future trends for research and development in this still expanding field are presented in a critical view of advantages and disadvantages as well as improvement of the validation of analytical procedures. The creation of new certified reference materials (CRMs) and validated methods for specified analytes in complex matrices is a demanding task in the coming years. Tailor-made solvents with physicochemical properties for intended use are required for the selective extraction and separation and open numerous possibilities and huge potential for future research and industrial applications.

Different greenness assessment perspectives for stability-indicating RP-HPLC method used for the assay of isoxsuprine hydrochloride and four nephrotoxic and hepatotoxic photothermal degradation products

BackgroundMilk is an important dietary source for a healthy and balanced diet, owing to its rich content of proteins, fats, sugars, vitamins, and minerals. Due to the importance of milk macronutrient content for consumers’ preferences, a multiplex metabolomics-based approach using Fourier-transform infrared spectroscopy (FTIR) and gas chromatography-mass spectrometry (GC-MS) fingerprinting platforms was employed for the characterization of metabolites in different types of buffalo (BM), cow (CM), goat (GM), and camel (LM) milk.MethodsGC-MS and FTIR coupled to chemometric tools (multivariate data analysis) were employed for the discriminative qualitative and quantitative analysis of BM, LM, CM, and GM milk, targeting their primary metabolites. A side-by-side comparative assessment of the performance of both the FTIR and GC-MS methods was implemented in the light of green analytical chemistry principle (GAC) and white analytical chemistry principles (WAC) using the 12 green analytical chemistry principles (12 GAC), analytical greenness metric approach (AGREE), national environmental methods index (NEMI), eco-scale assessment (ESA) and complementary green analytical procedure index (ComplexGAPI), and the red green blue (RGB) 12 algorithms.ResultsThe milk types were qualitatively identified by visual inspection of their characteristic FTIR spectra as a fingerprint for each milk type. Quantitatively, GC-MS revealed the presence of 87 peaks belonging to alcohols, amino acids/nitrogenous compounds, fatty acids, organic acids, sterols, sugars, and vitamins. Sugars, mainly lactose, appeared as the major component in all milk types. The highest lactose content was detected in CM 1.07-fold higher than LM making LM a potential alternative for lactose intolerance. Both BM and CM were found to contain the highest organic acid content 5.2-fold higher than that in LM, accounting for their acidity (sourness), while the lowest level was found in LM. On the other hand, LM had the highest vitamins content compared to other milks. Lastly, FTIR outperformed GC-MS in terms of greenness and whiteness, suggesting its utilization as an alternative to traditional chromatographic techniques such as GC-MS.

Paracetamol is one of the most widely consumed analgesic and antipyretic medications worldwide. It is frequently analyzed in many quality control (QC) laboratories in pharmaceutical companies, either in raw materials or drug products. It was reported that paracetamol self-toxicity often occurs, leading to the frequent analysis of paracetamol in toxicological centers in biological fluids. Green analytical chemistry (GAC) is growing to be a global philosophy; therefore, the high frequency of paracetamol analysis poses potential concerns. Chromatographic analytical methods used for the daily analysis of paracetamol could be a potential risk to the environment or the health of the analysts if not thoroughly considered. The presented study aims to establish greenness assessments of nine HPLC methods used to assay paracetamol in raw materials and drug products and twenty-one HPLC methods. The reason for selecting HPLC methods of analysis to be the core of the study is the known reproducibility, reliability and availability in most QC laboratories. The most commonly used metric systems for greenness evaluation are the Analytical GREEnness (AGREE), the eco-scale assessment (ESA) and the national environmental methods index (NEMI) which have been used in this comparative study. The greenest chromatographic method for the analysis of paracetamol in raw materials and drug products was introduced by Rao et al. (the obtained scores were ESA = 76 and AGREE = 0.62, while the greenest chromatographic method for the analysis of paracetamol in biological fluids was proposed by Modick et al.). The obtained scores were ESA = 85 and AGREE = 0.7. The NEMI tool proved to have limited performance compared to other metric systems, hence it could not be used alone. Accordingly, the collaboration of NEMI results with ESA and AGREE for greenness assessment is highly recommended to reach appropriate conclusions.

The pharmaceutical industries are focusing on Green Analytical Chemistry principles like miniaturization, eco-friendly solvent usage, waste recycling, and analyst safety for sustainable results. A simple, eco-friendly sensitive and effective extraction and multivariant green analytical method to estimate ketoconazole in bulk and cream formulation were developed and validated according to International Council for Harmonisation (ICH) guidelines. Based on the multivariant analytical technique, the developed method built in linear regression equations between concentration and absorbance with seven different wavelengths. The validation results represent the method has linear at a concentration of 12.8-19.2 μg mL-1 with calculated Limit of Detection (LOD) and Limit of Quantification (LOQ) of 0.338 and 1.026 μg mL-1, respectively. The method results representing a precise accuracy, inter-day, and intraday precision in all the wavelengths with percentage Relative Standard Deviation (RSD) under the limits as less than 2. Also, the method was tested with two different marketed ketoconazole cream formulations with a satisfactory result. The results of the proposed method replicated the novelty in classic approaches and proved statistically. This method was confirmed as greenest than previous methods reported by using assessing tools like National Environmental Method Index (NEMI), Green Analytical Procedure Index (GAPI), Analytical eco-scale, and Analytical Greenness (AGREE) metrics. As a result, the proposed approach could widely utilize for an efficient green analytical methodology for the estimation of ketoconazole.

The release of a product in the consumer market requires an analysis by quality control. This sector makes use of reliable analytical methods, by high performance liquid chromatography (HPLC), spectrophotometry in the ultraviolet and visible regions (UV-Vis), spectrophotometry in the infrared region (IR) or thin layer chromatography (TLC), for example, to reach a result. The analysis conditions of most of these analytical methods currently still use toxic reagents, generate a greater amount of waste, sample preparation has more steps, the need for instrumentation and consumables in greater quantity, generating a cost and impact on health and the environment greater than if there were adoption of the Green Analytical Chemistry (GAC) and the White Analytical Chemistry (WAC). The objective of this review is to show the relationship of analytical choices for current pharmaceutical analyzes with the GAC and the WAC. Analytical methods can be evaluated for greenness and whiteness using tools such as the National Environmental Method Index (NEMI), Eco-Scale Assessment (ESA), Analytical Greenness Metric (AGREE) and Green Analytical Procedure Index (GAPI). The use of NEMI, ESA, AGREE and GAPI tools brings the objective evidence needed to discuss the greenness and whiteness of an analytical method, leaving the subjective level. Furthermore, semi or quantitative data facilitate the choice of an analytical method and its conditions, when the target is the concern with eco-efficiency.

Central composite design as an analytical optimization tool for the development of eco-friendly HPLC-PDA methods for two antihypertensive mixtures containing the angiotensin receptor blocker Valsartan: Greenness assessment by four evaluation tools

Green analytical chemistry (GAC) is developing quickly at the moment, necessitating the establishment of clear, succinct guidance in the form of GAC principles that will aid in greening laboratory operations. Because they fall short of analytical chemistry's requirements, the current green chemistry and green engineering principles need to be revised for application in GAC. This article presents a collection of 12 principles that will be crucial for GAC's future. These principles include some innovative ideas (like using natural reagents) as well as well-known ones (like reducing the use of energy and reagents and eliminating waste, risk, and hazard). The goal of green analytical chemistry is to make analytical processes safer for people and the environment. When evaluating the greenness of an analytical approach, a wide range of factors are taken into account, including the quantity and toxicity of reagents, waste generated, energy consumption, the number of procedural steps, miniaturization, and automation. The eco-scale assessment (ESA), the green analytical procedure index (GAPI), and the national environmental methods index (NEMI) are the three evaluation techniques. Keywords: Green chemistry, National environmental method index, Eco-scale assessment, Green analytical procedure index.

The principles of green analytical chemistry have led to the development of analytical procedures that are increasingly sustainable. Different metrics have been created for the evaluation of greenness, although determination of the green nature of new analytical methods remains challenging, including for extraction methods that involve the use of natural deep eutectic solvents (NADES). In this study, the following five chemical metrics for the evaluation of greenness were considered: National Environmental Methods Index (NEMI), Green Analytical Procedure Index (GAPI), Analytical Eco-Scale, Analytical GREEnness (AGREE), and White Analytical Chemistry (WAC). These methods were applied in evaluation of the environmental and sustainability characteristics of three different methods for the preparation of plant material samples: microwave-assisted extraction (MAE), ultrasound-assisted extraction (UAE), and microwave-assisted acid digestion (MW-AD). These methods employed different NADES as extraction solvents, as well as dilute nitric acid as an oxidizing agent, for the determination of As, Cd, Pb, and V by inductively coupled plasma mass spectrometry (ICP-MS). The NEMI metric found no differences between the MAE-NADES and UAE-NADES methods. The GAPI metric found differences between the MAE-NADES and UAE-NADES methods and identify the disadvantageous aspects of each step of the methods. The Analytical Eco-Scale and AGREE identified the MAE-NADES method as the greenest, while WAC-12 RGB indicated the UAE-NADES method as the greenest procedure. A detailed discussion is provided of the application of each metric, together with their differences and advantages.

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

The main goal of Green Analytical Chemistry (GAC) is to reduce the use of hazardous chemicals and waste generation in analytical procedures without compromising method performance. Over the years, several metrics tools were introduced to measure the environmental impact and greenness of analytical procedures. In this context, this paper aims to present an overview of the most used GAC metrics in analytical chemistry, highlighting their criteria, advantages, disadvantages, and comparing their applicability. After extensive research, the metrics selected to be addressed were: National Environmental Method Index (NEMI), Analytical Eco-scale, Modified Green Analytical Procedure Index (MoGAPI), and Analytical GREEnness Metric (AGREE). NEMI is one of the oldest GAC metrics, describing the greenness of the method by a simple pictogram. Analytical Eco-Scale is based on subtracting penalty points from a total score of 100 points. MoGAPI uses a pictogram made up of fifteen categories and a total score to display the greenness of the analytical procedure. AGREE is represented as a circular pictogram divided into 12 parts, where each part corresponds to a principle of GAC. Each discussed metric has its own advantages and disadvantages; however, AGREE stands out as the most widely used and comprehensive GAC metric, applicable to several techniques. Although time-consuming, ideally, the best approach is to apply all metrics in combination to gain as much information as possible.

Ivermectin (IVE) is an antiparasitic sold in the form of tablets, pastes, and injectable solutions. Neither the literature nor the official compendiums present an environmentally friendly method for analyzing the final IVE product by thin layer chromatography (TLC) assisted by digital images. This combination strengthens the advantages of cost, handling, time, execution and process optimization. Items, which the green and clean analytical chemistry values, and the National Environmental Methods Index (NEMI), Eco-Scale Assessment (ESA), Analytical GREEnness Metric (AGREE) and Green Analytical Procedure Index (GAPI) tools measure. The objective of this work is to develop and validate an eco-efficient, fast, economical and easy-to-perform method for analysis of IVE injectable solution by TLC assisted by digital images. Silica gel plate, microsyringe and ethyl acetate: ethanol (13:2, v/v) as mobile phase were used in the method. The pixels were analyzed by Image J software after the spots were photographed under UV light. The method was selective when comparing standard and sample, indicative of stability by forced degradation test, linear (100-900 µg/mL), precise (RSD < 2%), accurate and rugged to modifications in the analytical process. The method was able to quantify commercial products, showing an average content of 98.95%. The greenness of the developed method presented NEMI with 4 green quadrants, ESA and AGREE with a score of 83 and 0.61, respectively, and GAPI predominantly green and yellow. The method was selective, indicative of stability, linear, precise, accurate, rugged and green, by NEMI, ESA, AGREE and GAPI, to quantify IVE in injectable solution. Additionally, it combined the advantages of TLC and digital image analysis. The work shows a TLC method assisted by digital images for analysis of ivermectin-based product.

How environmentally friendly is the analytical process? A paradigm overview of ten greenness assessment metric approaches for analytical methods

Special attention is given to the pharmacological treatment of combined medication of Carvedilol and hydrochlorothiazide which is the most effective and the most beneficial therapy for hypertensive patients with diabetes and various metabolic comorbidities. This work represents spectrophotometric platform scenarios based on factorized spectrum (FS) using interpoint data difference resolution scenarios (IDDRS) coupled with spectrum subtraction method (SS) for the concurrent quantification of carvedilol (CAR) and hydrochlorothiazide (HCT) when present together in a combination without the need for any initial physical separation steps. This IDD resolution scenario based on manipulating the zero-order spectra (D0) of both drugs in the mixture with various spectral features at different wavelength regions (200–400 nm), region I (220–250 nm), region II (240–300 nm) and region III (270–320 nm) via absorbance resolution (AR) and induced absorbance resolution (IAR) methods coupled with corresponding spectrum subtraction (SS). The calibration curves were established across the linearity ranges of 2.0–12.0 µg/mL at 242.50 nm and 4.0–40.0 µg/mL at 285.5 nm for CAR and 1.0–11.0 µg/mL at 226.10 nm and 2.0–20.0 µg/mL at 270.5 nm for HCT. Moreover, methods’ validation was confirmed via ICH guidelines. A Multicenter comparison between sensitivity, specificity in respect resolution sequence were applied using different wavelength regions with various concentration ranges was applied and finally spectral resolution recommendation is issued and cumulative validation score (CVS) is calculated as an indicator in the risk analysis. In quality control laboratories, the studied approaches are applicable for conducting analysis on the mentioned drugs. In addition, the selection of spectrophotometry aligns with the principles of green analytical chemistry, an approach that resonates with the overarching theme of minimizing environmental impact. Via four metric tools named: analytical greenness (AGREE), green analytical procedure index (GAPI), analytical eco-scale, and national environmental method index (NEMI), methods’ greenness profile was guaranteed.