Department of Pharmaceutical Analysis, KMCH College of Pharmacy, Coimbatore, Tamil Nadu 641048
Green analytical chemistry, or GAC, has become a key strategy for reducing the environmental effect of analytical procedures while preserving analytical dependability and efficiency. In the framework of sustainable pharmaceutical and environmental studies, this review offers a thorough summary of the core ideas, development, and future prospects of GAC. The fundamental ideas of GAC are covered in the article, with a focus on lowering the use of dangerous reagents, energy use, and waste production during analytical processes. The characteristics of green solvents and the several eco-friendly solvents currently used in analytical chemistry are specifically discussed. Additionally, popular green analytical chemistry criteria are emphasised to measure the environmental performance of analytical techniques, including analytical eco-scale and greenness assessment tools. The review also includes information about the contemporary green sample preparation methods and offers a comparative analysis of the methods based on efficiency, consumption of solvents, and environmental effects. In addition, the historical development of GAC and recent technological advancements in the area are discussed, which show the progress toward green analytical chemistry. This review has highlighted the increased relevance of GAC in the development of environmentally friendly analytical methodologies in the fields of pharmaceutical and environmental chemistry.
Green chemistry gave rise to the relatively new field of green analytical chemistry (GAC). The goal of the GAC concept, which was first presented in 2000, was to lessen or completely eradicate the detrimental effects of analytical processes on the environment, human health, and safety.[1]
Adopting best practices, such as minimising reagent usage, preferentially using non-hazardous and biodegradable reagents, energy management, reducing waste, removing elements that could endanger the researcher or analyst, and gradually enlarging the degree of integration, modernization, miniaturisation, and manageability of analytical instruments and methodologies, would be necessary for the effective application of GAC principles.[5]
Analyst who wanted to Incorporating sustainability into analytical framework, first proposed GAC as a straightforward concept. It has developed into a reputable field of study with many real-world accomplishments and a strong base of basic theories over time. [3] Since different analytical techniques have different levels of greenness, an evaluation of the analytical procedures' greenness is crucial. The Greenness evaluation metric [6]
Assesses how environmentally friendly the proposed approach is. A number of tools and software have been developed to assess how analytical methods affect the environment and operator health and safety. The metrics are especially helpful for comparing and choosing the greenest analytical methods, and they typically vary in complexity.[4]
2. PRINCIPLE:
Paul Anastas and John Warner defined and codified "green chemistry" in the late 1990s. It is based on twelve fundamental principles that, when combined, aim to make chemical processes more socially acceptable, economically sound, and sustainable. Particularly in sectors like the pharmaceutical industry, where safer, more effective, and environmentally friendly processes are of utmost importance, the principles act as a road map for transforming traditional methods of synthesis. [2].
The 12 principles of GAC are as follows:
‘‘Green Chemistry is the use of chemistry techniques and methodologies that reduce or eliminate the use or generation of feedstocks, products, by-products, solvents, reagents, etc. that are hazardous to human health or the environment’’. It is, in essence, the application of chemistry to the prevention of pollution. Analytical laboratories (GAC) previously developed the same Green Chemistry philosophy and concepts. [7]
Three main strategies are frequently used to prevent the negative environmental effects of analytical methods: minimising the number of solvents needed for sample pre-treatment; lowering the quantity and toxicity of reagents and solvents used in the measurement step—often accomplished through automation and miniaturisation; and creating alternative direct analytical techniques that completely do away with the need for reagents or solvents. [8]
Tab:1[2] The principles of green analytical chemistry expressed as the mnemonic SIGNIFICANCE:
|
Select direct analytical technique when possible. -Avoids complex sample preparation and extra steps. |
S |
The mnemonic SIGNIFICANCE represents the fundamentals of green analytical chemistry. |
I |
Increase safety for the operator Minimize exposure to hazardous fumes and physical risks. Ergonomic workstations. |
|
Integrate analytical processes and operations -Streamlines workflow, reducing human error and time per analysis. |
I |
C |
Carry out in-situ measurements Real-time field analysis. Eliminates sample transport and deterioration. |
|
|
Generate as little waste as possible and treat it properly -Emphasizes source reduction. Focuses on proper containment and treatment of necessary waste. |
G |
A |
Avoid derivatization Simplifies chemical reactions. Minimizes side-product formation and purification steps. |
|
|
Never waste energy -Optimizes instrument start-up and sleep cycles. Favors low-power equipment. |
N |
N |
Note sample number and size should be minimal Reduce collection scale and analytical aliquot. Uses smaller sample quantities. |
|
|
Implement automation and miniaturization of methods -Increases sample throughput. Enables portability and reduces reagent consumption.
|
I |
C |
Choose multi-analyte or multi-parameter methods Determine multiple compounds (e.g., metals, organics, pH) in a single run. Improves efficiency. |
|
|
Favor reagents from renewable sources -Use bio-based solvents, bio-enzymes, etc. Reduces dependency on petroleum-based chemicals. |
F |
E |
Eliminate or replace toxic reagents Switch to water, ethanol, or less hazardous reagents. Protects environmental and public health. |
3. EVOLUTION OF GREEN ANALYTICAL CHEMISTRY:
However, the process of rapid industrialization and population increase has contributed to the development of the economy but has also led to pollution and the exploitation of resources. Global environmental protection was initiated by the United Nations Scientific Conference on the Conservation and Use of Resources in 1949[30]. The Biosphere Conference in 1968, highlighting the importance of the scientific management of resources. Silent Spring was published in the 1960s and influenced the policy changes related to chemical pollution (Lutts, 1985). In 1972, the Stockholm Conference was the first international effort to address the environmental degradation issues that had begun to affect the planet. Later, the Brundtland Report was introduced in 1987 as sustainable development. In 1991, the U.S. Environmental Protection Agency introduced pollution prevention strategies that later became known as the concept of Green Chemistry in 1992. This led to the introduction of Green Analytical Chemistry as a means of sustainable development. [27]
[2]1962 - The environmental movement was initiated in with the publication of Rachel Carson’s book Silent Spring, which highlighted the adverse effects of chemicals on the environment
1972 - A significant advancement in federal environmental supervision was the establishment of the U.S. Environmental Protection Agency (EPA)
[27]1990 -"The term 'Green Chemistry' was officially coined in the title of a publication
1998 - Paul Anastas and John Warner created a seminal framework for sustainable chemistry in the 1990s, defining 12 principles to guide eco-friendly chemical design.
[25] 2001-2002 - GAC term was introduced and NEMI data base was established for green analytical methods.
2011-2012 - AMVI and Analytical Eco-scale have been launched to help quantify method greenness.
2013 - Remodeling the twelve principles of Green Chemistry, to recommended fit the Green Analytical Chemistry
2018 - GAPI was developed to assess full analytical workflows with visual pictogram
2020 - AGREE metric was introduced, aligning with twelve principles of green analytical chemistry
2021 - complexGAPI and RGB twelve algorithm expanded greenness evaluation tools and visualization.
2022 - AGREEprep was launched as the first metric focused on sample preparation greenness.
2024 - MoGAPI and complexMoGAPI introduced scoring and visualization enhancements to GAPI.
2025 - AGSA and Carbon footprint reduction index reflect growing focus on climate impact
4. PROPERTIES OF GREEN SOLVENTS IN ANALYTICAL CHEMISTRY
An idealized solvent with fine dissolution properties, selectivity, and extraction effectiveness should meet the following requirements: low toxicity, biodegradability, reusability, easily obtained from renewable sources, environmentally safe, and low cost.[9]
Gu and Jerome proposed a list that a Green Solvent needs to meet [10]
|
Availability |
Biodegradability |
|
Low price |
High performance |
|
Recyclability |
Stability |
|
Technical grade |
Low toxicity |
|
Easy synthesis |
Safe storage |
Tab:2 [10] – Classification of green solvents
|
TYPES OF GREEN SOLVENTS |
Water as solvents |
Used for efficient and Sustainable extraction |
|
Ionic liquids |
Compounds composed of entirely of ions offering potential as green solvents |
|
|
Supercritical Fluids |
Fluids used in effective extraction procedures that are above their critical temperature and pressure |
|
|
Deep Eutectic solvents |
combination of a donor and an acceptor of hydrogen bonds. |
|
|
Bio-based solvents |
Solvents derived from renewable and natural resources. |
The idea behind "green solvents" is to reduce the negative effects that solvent use in the manufacturing of chemicals has on the environment. It also takes into account the energy needed to produce solvents and the possibility of energy recovery at the end of their useful lives [11].
A total of fifty-eight (58) solvents were evaluated based on solvent selection guides [28]. These included (I) forty-nine (49) common and less common solvents used for, for example, spectroscopy, sample preparation, separation, with the goal of, for example, analysis, sample preservation, solvent exchange, and derivatisation, and (II) nine (9) deuterated solvents used in, for example, NMR spectroscopy.[11]
Tab:3 [12] Important Green Solvents Involved in GAC.
|
Solvent |
Advantages |
Challenges (Compress |
|
Ethanol (EtOH) |
Biodegradable; less toxic than ACN/MeOH; low vapor pressure; economical |
High viscosity → increased backpressure |
|
Propylene Carbonate (PC) |
CO?-derived; strong solvating power; UV cutoff ~210 nm |
Limited water miscibility (improved with EtOH/MeOH) |
|
Glycerol |
Non-volatile; non-flammable; renewable; UV cutoff ~207 nm; water miscible |
Very high viscosity; requires dilution/sonication |
|
Water |
Eco-friendly; no disposal issues; low cost; suitable for high-temperature LC |
Requires stable stationary phases for subcritical water LC |
|
Surfactants (MLC) |
Low toxicity; biodegradable; modify stationary phase polarity; reduces organic solvents |
Removal needed after analysis; limited compatibility |
|
Isopropanol (2-Propanol) |
Lower toxicity; good elution strength; sharp peaks; low UV absorbance |
Possible UV interference; column compatibility needed |
|
Acetone |
Biodegradable; strong elution strength; short analysis time; low viscosity |
High UV cutoff (~330 nm); possible backpressure |
|
Ethyl Acetate |
Less toxic; biodegradable; inexpensive; suitable for non-polar analytes |
UV cutoff ~260 nm; may increase pressure |
|
Methanol (MeOH) |
Good solvent strength; biodegradable; widely available |
Toxic if ingested; skin absorption; volatile |
|
Butanol |
Biodegradable; water miscible; cost-effective |
Higher viscosity; limited UV detection use |
|
Tetrahydrofuran (THF) |
Strong elution strength; useful for polymers; water miscible |
Peroxide formation risk; relatively toxic |
The representation shows how solvents frequently used in analytical chemistry are categorised according to how they affect the environment. Water and alcohols, such as methanol, ethanol, propanol, and butanol, are among the most ecologically friendly (green) solvents because of their superior biodegradability and reduced toxicity. Ethyl acetate, methyl acetate, acetone, and isopropanol are examples of moderately green solvents that provide a balance between environmental safety and performance. Because of their moderate effects, solvents like acetic acid that have a medium environmental impact should be used carefully. Because of their volatility and persistence, less environmentally friendly hydrocarbon solvents—such as cyclohexane, heptane, xylenes, limonene, pentane, toluene, and pinene—show greater environmental concerns. While dangerous solvents like carbon disulphide and benzene provide serious health and environmental risks, solvents like acetonitrile and methyl tert-butyl ether (MTBE) are thought to have a greater environmental impact. Chlorinated solvents, which are extremely toxic, persistent, and harmful to human health and the environment, make up the most dangerous category.[28]
5. GREEN ANALYTICAL CHEMISTRY METRICS:
The Green Analytical Chemistry metrics are quantitative or semi-quantitative ways to assess how safe, effective, and environmentally sustainable analytical processes are. Analytical scientists can use the Green Analytical Chemistry metrics to assess how well an analytical process complies with the principles of Green Analytical Chemistry, particularly when it comes to reducing the use of hazardous reagents, solvents, energy, and waste. Analytical scientists can assess chances to optimise conventional methods, particularly in pharmaceutical, environmental, and food analyses, as well as the distinctions between more ecologically friendly and conventional methods by using the evaluation criteria [30]. The development of green metrics was motivated by the realization of analytical laboratories that traditional assessment criteria, such as accuracy, precision, sensitivity, and robustness, were insufficient to evaluate the environmental impact of analytical procedures. As a result, a number of green assessment measures have been put out.[13]
Tab:4 [13,14] Evaluation Tools for Greenness Assessment in Analytical Methods
|
Metric |
Primary Goal |
Key Parameters considered |
Output / Scale |
|
AGREE (Analytical Greenness) |
Overall assessment of analytical method "Greenness" |
Holistic view; covers all 12 GAC principles. |
Score 0–1 with circular color pictogram (red–green) |
|
AMGS (Analytical Method Greenness Score) |
Process Efficiency |
Focuses on energy, waste, and solvent SHE index. |
Numerical score (lower = greener) |
|
Analytical Eco-Scale |
Measures method greenness using a penalty-point system. |
Solvent/reagent hazards, energy use, occupational hazards, waste amount, and waste treatment. |
Score = 100 – penalty points; >75 excellent, 50–75 acceptable, <50 poor greenness. |
|
BAGI (Blue Applicability–Green Index) |
Evaluates method greenness and practicality. |
10 criteria based on white analytical chemistry principles. |
Score 25–100 with colour scale and pictogram; higher score = greener method. |
|
ChlorTox Scale Chloroform-oriented Toxicity Scale) |
Toxicity evaluation relative to chloroform |
Benchmarks hazards against a known standard (Chloroform). |
Relative toxicity index |
|
CHEMS-1 model |
Overall chemical hazard assessment |
Emphasizes volatility and environmental persistence. |
Total Analytical Hazard Value (taHV) and Procedure Hazard Value (pHV) |
|
HEXAGON |
Quantitatively evaluates method greenness. |
Residues, carbon footprint, cost, toxicity/safety, and analytical performance. |
Hexagon diagram with scores 0–4; lower score = greener method. |
|
NEMI (The National Environmental Methods Index) |
provides a brief qualitative assessment of how environmentally friendly analytical techniques constitute. |
PBT chemicals, hazardous reagents, corrosiveness (pH <2 or >12), and waste generation (<50 g). |
Four-quadrant circle; quadrants turn green when criteria are satisfied, giving a simple visual assessment. |
|
GAPI (Green Analytical Procedure Index) |
Estimate the overall environmental impact across all analytical stages. |
NFPA hazard classification, waste, operator safety, instrumentation, solvents and reagents, and sample preparation. |
Colour pictogram: Green (low), Yellow (medium), Red (high impact); NFPA scale 0–4. |
|
RGB Model (White Analytical Chemistry) |
make available a comprehensive evaluation of analytical methods considering performance, greenness, and practicality. |
Red: Analytical performance, Green: Environmental safety, Blue: Practical and Economic aspects. |
Colour Score (0–100%): 66.6–100 satisfactory, 33.3–66.6 tolerable, 0–33.3 unsatisfactory. |
Based on the criteria and within the bounds of the assessment metrics, every strategy is eligible for greater greener ratings. When it comes to greener metrics, all of the developed methodologies are good. A few techniques are important; although, they may be improved with a little lower grade. The researcher may find it difficult to assess and adjust this using more modern reagents or solvents that use less energy, resulting in a more effective process that may be more ecologically friendly. Depending on the conditions, the score must be near either 100 or 1.[15]
6. GREEN SAMPLE PREPARATION TECHNIQUES:
Green sample preparation is now required to address the detrimental effects of traditional methods on the environment and human health. The main operational definition of "green sample preparation" is "Any analytical method that reduces or eliminates the use of hazardous solvents and promotes sustainability." Along with reducing waste and solvent consumption, the movement aimed to advance sustainable development in scientific practice [29]. This design compares significant approaches and their practical applications with a focus on solvent reduction, energy economy, scalability, and method reproducibility. Specifically, by dividing green sample preparation processes into macro and micro extraction methods, solvent reduction, extraction efficiency, repeatability, energy consumption, and waste minimisation were evaluated. [16]
Fig:1 Green sample preparation techniques
The field of sample preparation is evolving to meet application needs and the latest developments in Green Analytical Chemistry (GAC) concepts. In particular, since microextraction methods first appeared thirty years ago, they have changed, utilising more environmentally friendly and sustainable ingredients and solvents. This article explains the rationale for this tendency and summarises the key developments in this field, highlighting their characteristics and enhancements.[18]
Tab: 5 [17] Comparative analysis of green sample preparation techniques.
|
Extraction Technique |
Principle |
Green Aspects |
Advantages |
Limitations |
|
Accelerated Solvent Extraction (ASE) |
Extraction using high temperature and pressure in sealed cells. |
Uses much less solvent and shorter extraction time than Soxhlet. |
Fast, automated, efficient extraction. |
Requires specialized high-pressure equipment. |
|
Solid Phase Microextraction (SPME) |
Fiber coated with sorbent extracts analytes from sample or headspace. |
Solvent-free technique with minimal waste generation. |
Simple, rapid, integrates sampling and extraction. |
Limited fiber lifetime and selectivity. |
|
Stir Bar Sorptive Extraction (SBSE) |
Sorptive coated stir bar extracts analytes during stirring. |
Requires little or no organic solvent. |
High extraction capacity and sensitivity. |
Limited coating options; desorption step required. |
|
Thin-Film Microextraction (TFME) |
Thin sorptive film extracts analytes due to large surface area. |
Solvent-free or minimal solvent consumption. |
Faster extraction and good sensitivity. |
Limited commercial availability. |
|
Single Drop Microextraction (SDME) |
Micro-droplet of solvent extracts analytes from sample. |
Uses microlitre volumes of solvent, reducing waste. |
Simple, inexpensive, low solvent usage. |
Droplet instability and limited capacity. |
|
Liquid Phase Microextraction (LPME) |
Analytes partition into a small solvent phase through membrane/ interface. |
Very small solvent volume compared to LLE. |
High enrichment and low cost. |
Method optimization required. |
|
Supercritical Fluid Extraction (SFE) |
Uses supercritical CO? under pressure to extract analytes. |
Eco-friendly solvent (CO?) with minimal toxic solvent use. |
Rapid, selective and clean extraction. |
Expensive instrumentation. |
7. FUTURE PERSPECTIVES TOWARDS GREEN CHEMISTRY:
Green measurements will advance together with the growth of green chemical principles. It's possible that new measures will emerge to assess the sustainability of analytical techniques throughout the whole drug development process, in addition to their greenness. Green analytical technologies will become more and more integrated into routine pharmaceutical processes in the upcoming years. Pharmaceutical discovery, quality assurance, and stability testing will employ greener substitutes for conventional methods more frequently, such as MAE, SFC, and green solvents. Consequently, these indicators will be used by more regulatory bodies. This will guarantee uniform implementation across the sector and help standardise the concept of greener drugs. GAC has the potential to drastically alter the pharmaceutical sector by enhancing the efficiency, affordability, and environmental sustainability of analytical processes. Using GAC in pharmaceutical analysis has several advantages, including decreased waste, reduced solvent consumption, energy savings, and increased safety. Artificial intelligence, automation, miniaturisation, and real-time monitoring are key components of the upcoming of green analytical chemistry. Each of these elements makes a significant contribution to the industry's sustainability objectives. This approach also mirrors global trends toward greener and more sustainable practices across various sectors [19].
The future perspectives of green chemistry (GC) will be comprehensive more critically in various research fields which includes [20]
Since it gives scientists excellent chances to advance, the green chemistry educational system is still an open research subject and offers a solution to the present environmental problems. Active participation is crucial for ongoing GC practice improvement, which will have a good impact on lives and help create a sustainable future.[23]
8. GREEN CHEMISTRY AND ENVIRONMENTAL SUSTAINABILITY:
Green chemistry (GC) is an approach to deal with environmental problems associated with chemicals, processes, or stages of reactions. This approach is based on lowering the use and synthesis of dangerous chemicals in processes. The chemical risks section of the GC concept addresses a variety of health and environmental risks, physical hazards, toxicity, depletion of natural resources, and climate change. By examining the application of various chemical principles in the design or synthesis of chemicals, the GC seeks to minimise the use of dangerous substances that can endanger human health and protect the environment. The idea of sustainability was motivated by environmental and catastrophic disasters, as well as worries about resource depletion and chemical pollution. The basis of sustainability is the triple-bottom-line paradigm of three domains: social, economic, and environmental.[21]
Sustainability topics could be included into other relevant courses to further integrate green chemistry principles throughout the analytical chemistry curriculum. For instance, courses on spectroscopy or chromatography can contain sections that concentrate on the design of more environmentally conscious techniques, including the use of energy-efficient equipment or eco-friendly solvents. [22]
Miniaturised procedures, solvent-free or solvent-reduced sample preparation, eco-friendly solvents, and sophisticated instrumental approaches are examples of green techniques that increase laboratory efficiency while guaranteeing accurate, precise, and dependable findings. These techniques enhance worker safety and lessen environmental impact while supporting routine testing, stability studies, and regulatory submissions in pharmaceutical quality control.[24]
Finally, as green chemistry affects the future of our globe, we need to have optimistic outlooks. Green chemistry is not limited to chemical analyses using less hazardous solvents. Green chemistry is not what this is. Green chemistry is a multifaceted mix of behaviours and mindsets. It minimises reagents, steps, expenses, and energy while considering the entire process. The researcher in this situation also needs to be taken into account. Due to they understand that a man by himself would never add the talents of a potent team, the organisations differentiate themselves based on the physical and emotional well-being of their collaborators.[27]
Researchers in this subject face important and difficult challenges because to the swift progress in environmental awareness and the strict regulations pertaining to the use of solvents, chemicals, and samples. As a result, creating and inventing more ecologically friendly analytical techniques is crucial. GAC's ideals are already being applied. In the near future, it is awaited that the WAC approach and its applications will be crucial in preserving sustainability and safeguarding the environment. Additionally, it will help advance safer, more sustainable, and ecologically friendly analytical and bioanalytical procedures. [5]
CONCLUSION
Green analytical chemistry is a revolutionary strategy for attaining sustainable analytical methods in the environmental and pharmaceutical industries. Without sacrificing analytical performance, it is feasible to drastically cut down on the usage of dangerous chemicals, energy use, and waste production by including principles of green chemistry into analytical workflows. The environmental profile of analytical procedures has been significantly improved by the evolution and utilization of green solvents as well as cutting-edge sample preparation techniques like solvent-free approaches and microextraction. The sustainability profile of analytical procedures has been significantly improved by their growth and utilisation of green solvents as well as cutting-edge sample preparation techniques like solvent-free approaches and microextraction. Additionally, the development of different greenness assessment criteria has made it possible for academics to methodically review and improve analytical techniques from a sustainability standpoint. The development of GAC is a reflection of ongoing improvements in environmental technology, instrumentation, and miniaturisation. In the future, the sustainability of analytical procedures will be further improved by the use of energy-efficient analytical instruments, automated systems, and greener solvents. All things considered, the implementation of GAC principles will be essential to the advancement of environmentally conscious pharmaceutical analysis and environmental monitoring while promoting global sustainability objectives.
REFERENCES
V S Thiruvengadarajan, A Rajasekaran, I Ponnilavarasan, N Tamilselvi, M Logeswaran, Green Analytical Chemistry: An overview of Principles, Evolution, Future Perspectives toward Sustainable Pharmaceutical and Environmental Analysis, Int. J. of Pharm. Sci., 2026, Vol 4, Issue 4, 545-556. https://doi.org/10.5281/zenodo.19410325
10.5281/zenodo.19410325