The Blue Component of Analytical Chemistry: Assessing the Practicality of Analytical Methods

The evolution of analytical chemistry toward sustainability has primarily focused on green principles, aiming to minimize environmental impact. However, a truly holistic evaluation of analytical methods also needs consideration of practical applicability. This article focuses on the blue dimension of white analytical chemistry (WAC), a concept introduced to complement green analytical chemistry (GAC) by incorporating analytical performance (red) and practical and economic aspects (blue). The blue component emphasizes operational simplicity, cost-efficiency, and time-efficiency, advocating for methods that are fast, economical, easy to use, and require readily available instrumentation and materials. We introduce the Blue Applicability Grade Index (BAGI) as a dedicated metric tool for assessing method practicality. BAGI evaluates 10 key criteria, including analysis type, number of analytes, sample throughput, automation, and reagent availability, providing a numerical score and a visual pictogram to quantify blueness. Through selected case studies, we demonstrate how BAGI can guide the development and selection of analytical methods that are not only environmentally friendly but also highly practical for applications in analytical chemistry.

Understanding the Blue Dimension in WAC

The principles of green analytical chemistry (GAC) as originally proposed by Gałuszka and associates (1) immediately captured the attention of the research community and became a reference point for developing more sustainable and environmentally friendly analytical methods. In this context, a plethora of new methodologies were developed aiming to replace traditional ones with profound environmental impact. Although most of them successfully exhibited a greener character (for example, by replacing chemicals with greener alternatives, or by reducing the consumption of organic solvents or the waste generation), their performance characteristics and practicality were neglected on many occasions. The selection of an analytical method cannot be guided by greenness only, and there are more attributes that should be systematically considered. To obtain a more holistic evaluation of analytical methods, the concept of white analytical chemistry (WAC) was introduced by Nowak and associates (2) as an extension and complement to GAC. WAC was inspired by the existing red-green-blue (RGB) model, and it extends the concept of GAC (described by the green color) to other primary colors (with redreflecting the analytical performance of a method, and bluerevolving around method practicality). In this case, the redness of the method is an outcome of its scope of application, sensitivity, accuracy, and precision, and its blueness is an outcome of its operational simplicity, cost- and time-efficiency, and other requirements.

When all demands are met, meaning that the method exhibits a green, blue, and red character, the principles of WAC are met, resulting in a final white color obtained by mixing the above-mentioned ones. But what are the defining qualities that truly make a method blue?

The blue component of WAC is mentioned to cover practical and economic aspects. In this frame, a blue method would preferably be rapid, economic, simple in operation, and require instrumentation and materials that can be commonly found in analytical chemistry laboratories. In this frame, blue methods should be optimized for speed, with the aim of reducing the total time required for analysis. This includes not only the measurement itself, but also sample preparation, which is known to be the most tedious and time-consuming step of the analytical scheme.

If possible, sample preparation would be completely avoided to ensure rapid operations. However, this is not possible most of the time, since most of the samples require different manipulation procedures to become compatible with the analytical instrumentation. Sample preparation protocols that enable parallel handling and provide enhanced sample throughput should be chosen. Together with their time efficiency, blue methods should be economic, requiring less expensive instruments and materials, as well as limited media and personnel. This implies that the method is cost-effective to produce reliable results. Generally, these methods should have minimum demands in terms of sample size, laboratory facilities, special equipment, and skills of personnel, making their use accessible even in lower resource quality control laboratories. Finally, the operational simplicity of such approaches should be emphasized. For example, through miniaturization and automation, the practical utility of these methods can be significantly enhanced (2). All things considered, method applicability should always be promoted together with greenness to ensure that analytical methods are not only environmentally friendly but also practical, robust, and suitable for real-world applications.

A Tool for Evaluating Practicality: Blue Applicability Grade Index (BAGI)

Over the past few years, multiple metric tools have emerged and been used by chemists to evaluate the performance of an analytical method. Examples of such tools include the National Environmental Method Index (NEMI) (3),Analytical Eco-Scale (4),Analytical Greenness Calculator (AGREE) (5), Green Analytical Procedure Index (GAPI) (6), Complementary Green Analytical Procedure index (ComplexGAPI) (7), Complex Modified GAPI (ComplexMoGAPI) (8), Analytical Greenness Metric for Sample Preparation (AGREEprep) (9) and Sample Preparation Metric of Sustainability (SPMS) (10). These tools evaluate different aspects of sampling, sample preparation, and instrumental determination in terms of environmental impact. The aim of greenness evaluation is to identify the strong and weak points of each method toward its continuous improvement. Today, many scientists use these tools regularly to decrease the adverse effects of analytical chemistry on the environment. However, until recently, the evaluation of method “redness” and “blueness” was not common, mainly due to the absence of metric tools specifically developed for these aspects. To overcome this obstacle, the Blue Applicability Grade Index (BAGI) was introduced in 2023 (11) as a metric tool for practicality assessment. BAGI has 10 different sets of criteria referring to sample preparation, instrumental determination, or both steps:

• Criterion 1: Analysis type
• Criterion 2: Type and number of analytes included in the analytical scheme
• Criterion 3: Analytical technique
• Criterion 4: Simultaneous sample preparation
• Criterion 5: Type of sample preparation
• Criterion 6: Sample throughput
• Criterion 7: Availability of reagents and materials
• Criterion 8: Need for preconcentration
• Criterion 9: Degree of automation
• Criterion 10: Sample amount

For each criterion, different attributes can be chosen, each of them corresponding to a numerical score of 10.0, 7.5, 5.0, and 2.5 points, corresponding to high, medium, low, and no practicality. At the end, BAGI provides a numerical score ranging between 25.0 and 100.0, while a score higher than 60.0 is recommended to undoubtedly claim a practical method. Together with the numerical score, an asteroid pictogram is generated with different sub-sections contributing to each of the ten criteria. The colour of this sub-section can be dark blue, blue, light blue, or white, indicating that the method received 10.0, 7.5, 5.0, and 2.5 points, respectively. Generally, BAGI favors both quantitative and confirmatory analytical methods developed for the analysis of more than 15 analytes (ideally belonging to different classes).

The possibility to avoid sample preparation or select on-site techniques is preferred. The simultaneous sample preparation of more than 95 samples at a time, resulting in a sample throughput of more than 10 samples per h, is also supported. Moreover, the complete automation of the analytical scheme based on novel technology, the avoidance of additional preconcentration steps, the utilization of common commercially available reagents, and simple, in operation portable instrumentation (such as, for example, smartphones) is promoted. Finally, as per sample amount requirement, it is recommended to use less than 10 mL (or g) of food and environmental samples, or less than 100 μL (or mg) of biological samples. This differentiation is attributed to the different sample availability and abundance between different types. Until now, the ability of BAGI to evaluate the practicality of different analytical methods has been demonstrated among others for the determination of per- and polyfluoroalkyl substances in food and water samples (12) and pesticides in fruit juice (13).

Application of BAGI to Selected Case Studies

Several recent studies have implemented the BAGI metric to evaluate the practical or blue dimension of their analytical methodologies (14-16) Below, three selected case studies are briefly summarized to illustrate how BAGI has been applied in practice.

The first case study (17) focused on the development and validation of an environmentally friendly and practical method for detecting pesticides and related contaminants in bee pollen, using ultrasound-assisted extraction with liquid chromatography and quadrupole-time-of-flight mass spectrometry (UAE-LC-QTOF-MS). The method enabled quantitative, confirmatory, and multi-residue analysis of 79 target compounds. It featured a straightforward ultrasound-assisted extraction protocol and supported the analysis of 2–4 samples per h. The method relied on readily available reagents, required minimal sample volume, and did not involve any preconcentration steps. Furthermore, its semi-automated nature, thanks to the use of an LC autosampler, enhanced its practical value. Overall, this method received a BAGI score of 82.5 (see Figure 1a), exceeding the 60-point benchmark and reflecting high practical applicability. The second study (18) presented a miniaturized method for profiling biogenic volatile organic compounds (BVOCs) from Spanish tree species using headspace solid-phase microextraction withgas chromatography-mass spectrometry with a quadrupole time-of-flight detector (HS-SPME-GC-QTOF-MS) combined with chemometric techniques. This qualitative, multi-component approach involved microextraction and allowed for one sample to be processed per hour, constrained by the chromatographic conditions. Although it used a specialized SPME fiber not typically found in standard laboratories, the method still offered notable advantages: small sample size, no preconcentration, and semi-automated analysis via a CombiPAL autosampler. These factors contributed to a BAGI score of 67.5 (see Figure 1b), confirming the method’s strong alignment with the blue dimension. The third example (19) described a feasible high-performance liquid chromatography with diode array detection (HPLC-DAD) method for the simultaneous quantification of a triple-drug cancer therapy in human plasma. The BAGI score for this protocol was 72.5 (see Figure 1c) according to its simplicity in sample preparation, capability to analyze four samples per hour, use of accessible reagents, no preconcentration steps, and low injection volumes.

References

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Natalia Manousi is with the Institute of Chemical Technologies and Analytics at the Vienna University of Technology, in Vienna, Austria. Adrián Fuente-Ballesteros, José Bernal, and Ana M. Aresare with I. U. CINQUIMA, in the Analytical Chemistry Group (TESEA) of the Faculty of Sciences at University of Valladolid, in Valladolid, Spain. Victoria Samanidouis with the Laboratory of Analytical Chemistry, with the School of Chemistry of Aristotle University of Thessaloniki, in Thessaloniki, Greece. Direct correspondence to:natalia.manousi@tuwien.ac.atand adrian.fuente.ballesteros@uva.es