White Analytical Chemistry: Balancing Performance, Sustainability, and Practicality in Modern Methods

Modern analytical science faces the critical challenge of balancing innovation and growth with environmental responsibility. White analytical chemistry (WAC) emerges as a holistic paradigm, extending beyond the eco-centric focus of green analytical chemistry (GAC) to encompass the full spectrum of analytical method development. This article traces the evolution from green chemistry principles to the comprehensive WAC framework, highlighting its red-green-blue (RGB) model. The RGB model evaluates analytical methods across three dimensions: green for environmental impact, red for analytical performance (such as sensitivity and accuracy), and blue for practical and economic considerations (such as cost, time, and simplicity). In this article, we discuss how WAC promotes a more complete assessment of sustainability in analytical processes, emphasizing aspects like waste prevention, energy efficiency, operator safety, and the development of advanced tools and metrics for evaluating method “whiteness.” This integrated approach is crucial for fostering truly sustainable and efficient analytical practices in scientific research and beyond.

Growth, innovation, and research bring many benefits, but they can also contribute significantly to pollution (1,2). During the last century, the large amount of waste generated led scientists to establish green chemistry principles aimed at minimizing waste and protecting both the environment and laboratory personnel, as shown in Table I. The main aim is to reduce or, better, eliminate hazardous chemical substances, without decreasing quality of the process and product (2,3). It is subsequently understood how one cannot talk about green chemistry without talking about analytical parts of a chemical process. Because analytical chemistry focuses on monitoring product quantity and quality, it too must be guided by green chemistry principles (3–5). Searching in literature green chemistry or green analytical chemistry (GAC), the growth in interest of them results evident and fortunately, we would add.

Anastas reported that in nature there is no waste, as we commonly describe it, because organisms and systems evolve continually to reuse it. Waste is a human- product, and this is the reason why it should be reduced or, taking inspiration by nature, reuse it (6).

From Green to White: The Evolution of Analytical Sustainability

As visible from these principles, green chemistry and GAC are focused on eco-friendly approach of the method, focusing also with green sample preparation principles (GSP) about separation and sample preparation steps, because of their high consumption of solvents and reagents (7). In their manuscript, Koel and co-authors focused the attention on the possibility to develop methods “good,” useful, and cheap, trying to match these characteristics with GAC, though doing so was not mandatory (7). Through this, the idea of white analytical chemistry (WAC) was born, with the term “white” intended to suggest pureness, combining quality, sensitivity, and selectivity with an eco-friendly and safe approach for analysts (8). The quality of an analytical method is defined by its sensitivity, selectivity, accuracy, and precision. On the other hand, cost and speed of analysis and ease to use method are practical considerations to ensure. The main aim of this newer approach (founded in 2021) is to give a more complete evaluation (8). Many researchers are trying to match their studies with WAC approach, even if it’s not mentioned, thanks to the wide approach.

The RGB Model: Red, Green, and Blue Dimensions Explained

WAC proposed a new approach, the red-blue-green (RGB) model, which consists of three independent dimensions, each covering a different aspect of analytical methods. The green part of the model envelops GAC principles (G1-G4), the red part is about analytical parameters and efficiency, and the blue principles are regarding practical and economical aspects. Specific parameters are reported in Table II. Red, green, and blue represent the primary aspects that a scientist needs to consider before validation. White is that method considered complete and coherent. When the three colors are mixed, the resulting shade reflects how consistently a method meets the combined principles. Instead, if a method is green, it is only similar to green chemistry principles; if red, it has good analytical parameters, and, finally, if it is blue, it is easy to use and not expensive. At the end, the final color will be a mixture of the three primary colors. This is helpful to understand which part of the method used could be modified or improved.

Why WAC Matters in Today's Analytical Landscape

Nowadays, it is fundamental to follow green chemistry principles, as is evident through the choice of mobile phases, solvent extraction, and volume of solvents extraction. In addition, many scientists are often choosing shorter stationary phases than in the past, and this approach permits a decrease in the time of separation; consequently, the generation of waste is reduced. Furthermore, sensitivity has improved, making it possible to achieve very low limits of detection and quantification. Continuous research permits to increase type of extraction, turning on micro-extraction techniques for which are not required high consumption of solvents. Examples of these techniques include fabric phase sorptive extraction (FPSE), magnetic SPE, magnetic nanoparticles, capsule phase microextraction (CPME), and ultrasound-assisted microextraction (9-13). The possibility of absorption, extraction, and elution of analytes in lower volume permits an increase in sensitivity, permitting quantification of low concentrations. Also, “dilute-and-shoot” is really used as sample preparation techniques, matching with WAC principles/ approach (14,15).

A Brief Overview of Metrics over Time and Tools

To evaluate the greenness of a protocol, many tools were developed in the last decade, aiming to be as standardized as possible. WAC overcomes problems with conventional tools such as the Green Analytical Process Index (GAPI) or ComplexGAPI, which deal with the different weight to green chemistry rules (16). Most common and firstly to be created as tools for greenness was life cycle assessment (LCA), with its main problem being that it is based on manager and organization principles (17). As overcoming these problems was too difficult using LCA, the National Environment Methods Index (NEMI) was born, showing an ease of use and comprehension, but an inability to give a quantification of the goodness of the method.

Following this, Analytical Eco-Scale was proposed, where, after giving or subtracting a point and then considering volume, type of solvents, and energy consumption, a numerical score is generated; scores above 75 indicate a green method, while those below 50 are considered unacceptable (18). Green Analytical Procedure Index (GAPI) and ComplexGAPI were respectively proposed in 2018 and 2021; these consider a variety of data, including waste and toxicity of solvents used. In ComplexGAPI, sample preparation and instrumentation are considered as well (19, 20). One of the most used is Analytical GREEnness (AGREE) which is based on 12 principles of green chemistry, with a color given for each of them; at the end of testing, a resulting pictogram with a point (from 0 to 1.0) and its respective color will appear (21). This was the first tool to be published, but in no way was it the last. For example, in 2024 Mansour and colleagues used GAPI to create a new tool, called Modified GAPI (MoGAPI), to highlight storage and transport information about sample preparation, number of samples and reagents, energy used (kWh), and total waste generated, providing a more comprehensive assessment (22). Manousi and associates focused their tool on the applicability of the method; for this reason, this tool was named Blue Applicability Grade Index (BAGI). BAGI considers three classes, with questions regarding analytical determination and sample preparation, as well as the number of analytes, type of analysis and instrumentation, and the automation. The generated pictogram is then colored with different shades of blue (23).

In 2025, many scientists published various tools, including Click Analytical Chemistry Index (CACI, which is based on feasibility, application, sample preparation, and sensitivity of the method) (24), and Analytical Green Star Area (AGSA, which considers automatization and miniaturization of the protocol, sample preparation, and size, as well as the safety of the operators) (25). There is also a Red Analytical Performance Index (RAPI), which was published in 2025 and considers reproducing, trueness, recovery, and matrix effect, as well as other analytical parameters (26). Finally, there is the Violet Innovation Grade Index (VIGI), which considers the innovation of the analytical method used (27).

Conclusion

The purpose of this article is to show and explain at what point scientists are at in matters concerning environmentally friendly chemistry. Environment is a pivotal point in the last decades, increasing in interest in researcher laboratories, and is sure to remain crucial for future research to avoid increases in environmental pollution. We have shown with the most recent tools that ensuring the health and safety of laboratory staff remains a major challenge, and that these tools provide a useful starting point for aligning environmental sustainability with safe research practices. This approach will certainly be an opportunity for growth in continuous research of materials and methods. Automatization and miniaturization of solvents and devices for performing analysis in situ perfectly match with these points. This multidisciplinary approach will present valuable challenges and inspire continuous improvement.

References

1. Castiello, C.; Junghanns, P.; Mergel, A. et al. GreenMedChem: The Challenge in the Next Decade Toward Eco-Friendly Compounds and Processes in Drug Design. Green Chem. 2023, 25, 2023, 2109-2169. DOI: 10.1039/D2GC03772F
2. Nowak, P. M. What Does it Mean That “Something is Green”? The Fundamentals of a Unified Greenness Theory. Green Chem. 2023, 25, 4625-4640. DOI: 10.1039/D3GC00800B
3. Koel, M.; Kaljurand, M. Application of the Principles of Green Chemistry in Analytical Chemistry. Pure Appl. Chem.2006, 78, 1993-2002. DOI: 10.1351/pac200678111993
4. Locatelli, M.; Perrucci, M.; Ali, I., et al. Green Analytical Methods and Principles of Green Analytical Chemistry. In Green Analytical Methods and Miniaturized Sample Preparation techniques for Forensic Drug Analysis; Elsevier. 2025, 3-21. DOI: 10.1016/B978-0-443-13907-9.00002-4
5. Perrucci, M.; Ricci, E. M.; Locatelli, M. et al. Recent Trends in Microsampling and Reduced-Volume Sample Preparation Procedures. Advances in Sample Preparation 2025, 100182. DOI: 10.1016/j.sampre.2025.100182
6. Anastas, P. T.; Zimmerman, J. B. The Periodic Table of the Elements of Green and Sustainable Chemistry. Green Chem. 2019, 21, 6545- 6566. DOI: 10.1039/C9GC01293A
7. Koel, M. Do We Need Green Analytical Chemistry? Green Chem. 2016, 18, 923- 931. DOI: 10.1039/C5GC02156A
8. Nowak, P. M.; Wietecha-Posłuszny, R.; Pawliszyn, J. White Analytical Chemistry: An Approach to Reconcile the Principles of Green Analytical Chemistry and Functionality. TrAC Trends Anal. Chem.2021, 138, 116223. DOI: 10.1007/s00216-022-04064-w
9. Tartaglia, A.; Kabir, A.; Ulusoy, S. et al. FPSE-HPLC-PDA Analysis of Seven Paraben Residues in Human Whole Blood, Plasma, and Urine. J. Chromatog. B.2019, 1125, 121707. DOI: 10.1016/j.jchromb.2019.06.034
10. Mandrioli, R.; Di Lecce, R.; Noreen, S. et al. Novel Microsampling Approach Using Fabric-Phase Sorptive Extraction (FPSE) for Cannabinoid Analysis in Blood. Microchem. J. 2025, 113855. DOI: 10.1016/j.microc.2025.113855
11. Ulusoy, S.; Locatelli, M.; Tartaglia, A. et al. Sensitive Determination of Anastrozole and Letrozole in Urine Samples by Novel Magnetic Nanoparticles Containing Tetraethylenepentamine (TEPA) Prior to Analysis by High-Performance Liquid Chromatography-Diode Array Detection. Chem. Papers 2022, 76, 3649-3659. DOI: 10.1007/s11696-022-02112-4
12. Manousi, N.; Kabir, A. Furton, K. G. et al. Exploiting the Capsule Phase Microextraction Features in Bioanalysis: Extraction of Ibuprofen from Urine Samples. Microchem. J. 2022, 172, 106934. DOI: 10.1016/j.microc.2021.106934
13. Pereira-Coelho, M.; da Silva Haas, I. C.; Vitali, L. et al. Dispersive Pipette Extraction and HPLC-DAD for the Determination of Polyphenols in Grape Juice. Food Anal. Methods 2024, 17, 269-283. DOI: 10.1007/s12161-023-02565-7
14. Merone, G. M., Tartaglia, A., Rossi, S. et al. Fast Quantitative LC-MS/MS Determination of Illicit Substances in Solid and Liquid Unknown Seized Samples. Anal. Chem. 2021, 93, 16308-16313. DOI: 10.1021/acs.analchem.1c03310
15. Almofti, N., Ballesteros-Gómez, A., Rubio, S. et al. Analysis of Conventional and Nonconventional Forensic Specimens in Drug-Facilitated Sexual Assault by Liquid Chromatography and Tandem Mass Spectrometry. Talanta 2022, 250, 123713. DOI: 10.1016/j.talanta.2022.123713
16. Locatelli, M.; Kabir, A.; Perrucci, M. et al. Green Profile Tools: Current Status and Future Perspectives. Advances in Sample Preparation 2023, 6, 100068. DOI: 10.1016/j.sampre.2023.100068
17. Pryshlakivsky, J.; Searcy, C. Life Cycle Assessment as a Decision-Making Tool: Practitioner and Managerial Considerations. J. Clean. Prod. 2021, 309, 127344. DOI: 10.1016/j.jclepro.2021.127344
18. Gałuszka, A.; Migaszewski, Z. M.; Konieczka, P. Analytical Eco-Scale for Assessing the Greenness of Analytical Procedures. TrAC Trends Anal. Chem. 2012, 37, DOI: 61-72. DOI: 10.1016/j.trac.2012.03.013
19. Płotka-Wasylka, J. A New Tool for the Evaluation of the Analytical Procedure: Green Analytical Procedure Index. Talanta 2018, 181, 204-209. DOI: 10.1016/j.talanta.2018.01.013
20. Płotka-Wasylka, J.; Wojnowski, W. Complementary Green Analytical Procedure Index (ComplexGAPI) and Software. Green Chem. 2021, 23, 8657-8665. DOI: 10.1039/D1GC02318G
21. Pena-Pereira, F.; Wojnowski, W.; Tobiszewski, M. AGREE—Analytical GREEnness Metric Approach and Software. Anal. Chem. 2020, 92, 10076-10082. DOI: 10.1021/acs.analchem.0c01887
22. Mansour, F. R.; Płotka-Wasylka, J.; Locatelli, M. Modified GAPI (MoGAPI) Tool and Software for the Assessment of Method Greenness: Case Studies and Applications. Analytica 2024, 5, 451-457. DOI: 10.3390/analytica5030030
23. Manousi, N.; Wojnowski, W.; Płotka-Wasylka, J. et al. Blue Applicability Grade Index (BAGI) and Software: A New Tool for the Evaluation of Method Practicality. Green Chem. 2023, 25, 7598-7604. 10.1039/D3GC02347H
24. Mansour, F. R.; Bedair, A.; Locatelli, M. Click Analytical Chemistry Index as a Novel Concept and Framework, Supported with Open Source Software to Assess Analytical Methods. Advances in Sample Preparation 2025, 14, 100164. 10.1016/j.sampre.2025.100164
25. Mansour, F. R.; Bedair, A.; Belal, F. Analytical Green Star Area (AGSA) as a New Tool to Assess Greenness of Analytical Methods. Sustain. Chem. Pharm. 2025, 46, 102051. DOI: 10.1016/j.scp.2025.102051
26. Nowak, P. M.; Wojnowski, W.; Manousi, N. et al. Red Analytical Performance Index (RAPI) and Software: The Missing Tool for Assessing Methods in Terms of Analytical Performance. Green Chem. 2025, 27, 2025, 5546-5553. DOI: 10.1039/D4GC05298F
27. Fuente-Ballesteros, A.; Martínez-Martínez, V.; Ares, A. M. et al. Violet Innovation Grade Index (VIGI): A New Survey-Based Metric for Evaluating Innovation in Analytical Methods. Anal. Chem. 2025, 97, 6946-6955. DOI: 10.1021/acs.analchem.5c00212

Marcelo Locatelli is with the Department of Science of the University “G. d’Annunzio” of Chieti-Pescara, in Chieti, Italy. Miryam Perrucci is with the Department of Biosciences and Agro-Food and Environmental Technologies at the University of Teramo, in Teramo, Italy, and the Department of Innovative Technologies in Medicine & Dentistry at the University “G. d’Annunzio” of Chieti-Pescara, in Chieti, Italy. Adrián Fuente-Ballesteros, José Bernal, and Ana M. Ares are with the Analytical Chemistry Group (TESEA), I. U. CINQUIMA, of the Faculty of Sciences at the University of Valladolid, in Valladolid, Spain. Direct correspondence to

marcello.locatelli@unich.itand adrian.fuente.ballesteros@uva.es