**2. Cornerstones of modern analytical chemistry**

Analytical Chemistry has evolved dramatically over the past few decades, from the traditional notion held for centuries to that of a modern, active discipline of Chemistry. Changes have revolved mainly around new ways of describing the discipline, and its aims and objectives, a broader notion of real basic references, the definition of the results of research and development activities and a holistic approach to analytical properties.

#### **2.1. Definition**

Analytical Chemistry can be defined in four simple ways as: (1) the discipline in charge of "Analysis" (the fourth component of Chemistry in addition to Theory, Synthesis and Applications, all of which are mutually related via the vertices of the tetrahedron in Figure 2); (2) the discipline in charge of the production of so named "(bio)chemical information" or "analytical information"; (3) the discipline of (bio)chemical measurements; and (4) the chemical metrological discipline, which is related to the previous definition.

**Figure 2.** Analytical Chemistry is a discipline of Chemistry (C) inasmuch as it is responsible for "Analysis", an essential component of Chemistry in addition to theory, synthesis and applications in different fields (e.g. environmental science, agriculture, medicine).

These four general definitions have been used to formulate various more conventional definitions such as the following:

"*Analytical Chemistry is a scientific discipline that develops and applies methods, instruments and strategies to obtain information on the composition and nature of matter in space and time*" (Working Party on Analytical Chemistry of the European Federation of Chemical Societies) [2].

"*Analytical Chemistry is a metrological discipline that develops, optimizes and applies measurement processes intended to produce quality (bio)chemical information of global and partial type from natural and artificial objects and systems in order to solve analytical problems derived from information needs*" [3].

The strategic significance of Analytical Chemistry arises from the fact that it is an information discipline and, as such, essential to modern society. Analytical Chemistry as a scientific discipline has its own foundations, which materialize in keywords such as information, metrology, traceability, analytical properties, analytical problems and analytical measurement processes. Also, it shares some foundations with other scientific and technical areas such as Mathematics, Physics, Biology or Computer Science.

#### **2.2. Aims and objectives**

94 Analytical Chemistry

obsolescent.

fields.

**2.1. Definition** 

Analytical Chemistry should in fact be present at a variety of interfaces such as those of Figure 1.1. Two belong to the realm of Chemistry (the framework of reference), namely:

1. *Internal interfaces* with other chemical areas (e.g. organic, inorganic, physical and applied chemistry, chemical engineering). Classifying Chemistry into these disciplines or subdisciplines, which are related via "fading" interfaces (1), has become

2. *External interfaces* with other scientific and technical disciplines such as biology, biochemistry, mathematics, physics or engineering, where Analytical Chemistry can play an active role (e.g. in the determination of enzyme activities or that of drugs of abuse in biological fluids) or a passive one (e.g. in chemometric developments for data

Also, if Analytical Chemistry is to be coherent with its foundations, aims and objectives (see Section 2.2. of this chapter), it should establish two-way relationships with a variety of international written standards (norms and guides) in order to contribute to the continuous improvement of human activities (see Figure 1.2). The classical relationship between Analytical Chemistry and quality has materialized in ISO 17025:2005, which is the reference for laboratory accreditation. This norm contains technical requirements and other, management-related specifications that are shared with those in ISO 9001:2008, which is concerned with quality in general. Also, written standards dealing with knowledge management and social responsibility are highly relevant to the foundations and applications of Analytical Chemistry, even though they have rarely been considered jointly to date. In addition, Analytical Chemistry is very important for effective environmental protection, and occupational health and safety, since the (bio)chemical information it provides is crucial with a view to making correct decisions in these two complementary

Analytical Chemistry has evolved dramatically over the past few decades, from the traditional notion held for centuries to that of a modern, active discipline of Chemistry. Changes have revolved mainly around new ways of describing the discipline, and its aims and objectives, a broader notion of real basic references, the definition of the results of

Analytical Chemistry can be defined in four simple ways as: (1) the discipline in charge of "Analysis" (the fourth component of Chemistry in addition to Theory, Synthesis and Applications, all of which are mutually related via the vertices of the tetrahedron in Figure 2); (2) the discipline in charge of the production of so named "(bio)chemical information" or "analytical information"; (3) the discipline of (bio)chemical measurements; and (4) the

research and development activities and a holistic approach to analytical properties.

chemical metrological discipline, which is related to the previous definition.

processing or the use of immobilized enzymes in analytical processes).

**2. Cornerstones of modern analytical chemistry** 

To be coherent with the previous definitions, Analytical Chemistry should have the aims and objectives depicted in Figure 3.

Analytical Chemistry Today and Tomorrow 97

**2.3. Basic analytical standards** 

concepts. For details, see text.

**2.4. R&D analytical "products"** 

Analytical Chemistry relies on the three basic standards (milestones) shown in Figure 4 [5]. The two classical standards, which have been around for centuries, are tangible measurement standards (e.g. pure substances, certified reference materials) and written standards (e.g. the norms and guides of Figure 1, official and standard methods). A modern approach to Analytical Chemistry requires including a third standard: (bio)chemical information and its properties it should have to facilitate correct, timely decisions. Without this reference, analytical laboratory strategies and work make no sense. In fact, it is always essential to know the level of accuracy required, how rapidly the results are to be produced, and the maximum acceptable cost per sample (or analyte), among other requirements.

**Figure 4.** Basic standards supporting the Analytical Chemistry building and analytical quality related

As can be seen in Figure 4, conventional basic standards are related to so named "metrological quality", whereas (bio)chemical information and its required characteristics (the third basic standard) are related to "practical quality". Combining both concepts in so named "integral analytical quality" requires balancing two contradictory forces, which in

The basic side of Analytical Chemistry encompasses a variety of R&D activities aimed at improving existing methods and/or developing new ones in response to new, challenging

turn entails the adoption of "quality compromises" (see Section 4 of this chapter).

**Figure 3.** Primary aims and objectives of Analytical Chemistry. For details, see text.

Analytical Chemistry has two essential aims. One, which is intrinsic, is the obtainment of as high metrological quality as possible (i.e. of as true as possible analytical information with as low as possible uncertainty). The other, extrinsic aim is solving analytical problems derived from (bio)chemical information needs posed by "clients" engaged in a great variety of activities (health, general and agrifood industries, the environment).

The main magnifying objectives of Analytical Chemistry are to obtain a large amount of (bio)chemical information of a high quality, and its main reducing objectives to use less material (sample, reagents), time and human resources with minimal costs and risks for analysts and the environment.

The aims and objectives of Analytical Chemistry share its two sides (basic and applied); these are usually in contradiction and require appropriate harmonization. Thus, ensuring a high metrological quality may be incompatible with obtaining results in a rapid, economical manner. In fact, obtaining more, better (bio)chemical information usually requires spending more time, materials and human resources, as well as taking greater risks. Balancing the previous two aims and objectives requires adopting quality compromises [4] that should be clearly stated before specific analytical processes are selected and implemented.

#### **2.3. Basic analytical standards**

96 Analytical Chemistry

**Figure 3.** Primary aims and objectives of Analytical Chemistry. For details, see text.

of activities (health, general and agrifood industries, the environment).

analysts and the environment.

selected and implemented.

Analytical Chemistry has two essential aims. One, which is intrinsic, is the obtainment of as high metrological quality as possible (i.e. of as true as possible analytical information with as low as possible uncertainty). The other, extrinsic aim is solving analytical problems derived from (bio)chemical information needs posed by "clients" engaged in a great variety

The main magnifying objectives of Analytical Chemistry are to obtain a large amount of (bio)chemical information of a high quality, and its main reducing objectives to use less material (sample, reagents), time and human resources with minimal costs and risks for

The aims and objectives of Analytical Chemistry share its two sides (basic and applied); these are usually in contradiction and require appropriate harmonization. Thus, ensuring a high metrological quality may be incompatible with obtaining results in a rapid, economical manner. In fact, obtaining more, better (bio)chemical information usually requires spending more time, materials and human resources, as well as taking greater risks. Balancing the previous two aims and objectives requires adopting quality compromises [4] that should be clearly stated before specific analytical processes are Analytical Chemistry relies on the three basic standards (milestones) shown in Figure 4 [5]. The two classical standards, which have been around for centuries, are tangible measurement standards (e.g. pure substances, certified reference materials) and written standards (e.g. the norms and guides of Figure 1, official and standard methods). A modern approach to Analytical Chemistry requires including a third standard: (bio)chemical information and its properties it should have to facilitate correct, timely decisions. Without this reference, analytical laboratory strategies and work make no sense. In fact, it is always essential to know the level of accuracy required, how rapidly the results are to be produced, and the maximum acceptable cost per sample (or analyte), among other requirements.

**Figure 4.** Basic standards supporting the Analytical Chemistry building and analytical quality related concepts. For details, see text.

As can be seen in Figure 4, conventional basic standards are related to so named "metrological quality", whereas (bio)chemical information and its required characteristics (the third basic standard) are related to "practical quality". Combining both concepts in so named "integral analytical quality" requires balancing two contradictory forces, which in turn entails the adoption of "quality compromises" (see Section 4 of this chapter).

#### **2.4. R&D analytical "products"**

The basic side of Analytical Chemistry encompasses a variety of R&D activities aimed at improving existing methods and/or developing new ones in response to new, challenging information needs. These activities can produce both tangible and intangible tools such as those of Figure 5 [6]. Typical tangible analytical tools include instruments, apparatus, certified reference materials, immobilized enzymes and engineering processes adapted to the laboratory scale (e.g. supercritical fluid extraction, freeze-drying). Analytical strategies, basic developments (e.g. calibration procedures) and chemometric approaches (e.g. new raw data treatments, experimental design of analytical methods) are the intangible outputs of analytical R&D activities. Transfer of technology in this context is more closely related to tangible R&D tools, whereas transfer of knowledge is mainly concerned with intangible R&D analytical tools; in any case, the two are difficult to distinguish.

Analytical Chemistry Today and Tomorrow 99

*Accuracy* is the degree of consistency between a result (or the mean of several) and the true value or that considered as true (viz. the value for a certified reference material) in quantitative analyses. Any differences between the two constitute systematic errors.

*Reliability* is the proportion (percentage) of right yes/no answers provided by independent tests for analyte identification in aliquots of the same sample in qualitative

*Representativenes*s is the degree of consistency of the results with the samples received by a laboratory, the overall sample or object studied, the particular analytical problem

*Precision* is the degree of consistency among a set of results obtained by separately applying the same analytical method to individual aliquots of the same sample, the mean of the results constituting the reference for assessing deviations or random errors.

*Robustness* in an analytical method is the resistance to change in its results when applied

*Sensitivity* is the ability of an analytical method to discriminate between samples containing a similar analyte concentration or, in other words, its ability to detect (qualitative analysis)

*Selectivity* is the ability of an analytical method to produce qualitative or quantitative

*Expeditiousness* in an analytical method is its ability to rapidly develop the analytical process from raw sample to results. Expeditiousness is often expressed as the sample

*Cost-effectiveness* is the monetary cost of analyzing a sample with a given method and is commonly expressed as the price per analyte-sample pair. This property has two basic economic components, namely: the specific costs of using the required tools and the

*Personnel-related factors.* Strictly speaking, these are not analytical properties but are occasionally essential towards selecting an appropriate analytical method. These factors include the risks associated to the use of analytical tools and the analyst's safety and

*Productivity-related properties* (expeditiousness, cost-effectiveness and personnel-related factors) are attributes of analytical processes with a very high practical relevance to most

to individual sample aliquots under slightly different experimental conditions.

or determine (quantitative analysis) small amounts of analyte in a sample.

results exclusively dependent on the analytes present in the sample.

*Basic analytical properties* (precision, robustness, sensibility selectivity) are attributes of analytical processes and provide support for capital properties. Thus, it is impossible to obtain highly accurate results if the analytical process is not precise, sensitive and selective

analyses.

analytical problems.

comfort.

and the information required by the client.

enough. These properties can be defined as follows:

frequency (i.e. in samples per hour or per day).

overhead costs of the laboratory performing the analyses.

**Figure 5.** Main outputs of research and development (R&D) in Analytical Chemistry, transfer of knowledge and technology included. For details, see text.

#### **2.5. Quality indicators**

Analytical properties are quality indicators for the great variety of systems, tools and outputs of (bio)chemical processes that allow one to compare and validate analytical processes and the results they provide. Traditionally, they have been dealt with separately, with disregard of the high significance of their mutual relationships. Figure 6 provides a holistic view of analytical properties [7] as classified into three groups (capital, basic and productively-related) that are assigned to analytical results and analytical processes.

*Top or capital analytical properties* (accuracy and representativeness) are characteristics of the quantitative results of measurement processes. Accuracy is related to two classical metrological properties: traceability and uncertainty. In qualitative analysis, this property must be replaced with "reliability", which includes precision (a basic property). Capital properties can be defined in simple terms as follows:

*Accuracy* is the degree of consistency between a result (or the mean of several) and the true value or that considered as true (viz. the value for a certified reference material) in quantitative analyses. Any differences between the two constitute systematic errors.

98 Analytical Chemistry

information needs. These activities can produce both tangible and intangible tools such as those of Figure 5 [6]. Typical tangible analytical tools include instruments, apparatus, certified reference materials, immobilized enzymes and engineering processes adapted to the laboratory scale (e.g. supercritical fluid extraction, freeze-drying). Analytical strategies, basic developments (e.g. calibration procedures) and chemometric approaches (e.g. new raw data treatments, experimental design of analytical methods) are the intangible outputs of analytical R&D activities. Transfer of technology in this context is more closely related to tangible R&D tools, whereas transfer of knowledge is mainly concerned with intangible

R&D analytical tools; in any case, the two are difficult to distinguish.

**Figure 5.** Main outputs of research and development (R&D) in Analytical Chemistry, transfer of

productively-related) that are assigned to analytical results and analytical processes.

Analytical properties are quality indicators for the great variety of systems, tools and outputs of (bio)chemical processes that allow one to compare and validate analytical processes and the results they provide. Traditionally, they have been dealt with separately, with disregard of the high significance of their mutual relationships. Figure 6 provides a holistic view of analytical properties [7] as classified into three groups (capital, basic and

*Top or capital analytical properties* (accuracy and representativeness) are characteristics of the quantitative results of measurement processes. Accuracy is related to two classical metrological properties: traceability and uncertainty. In qualitative analysis, this property must be replaced with "reliability", which includes precision (a basic property). Capital

knowledge and technology included. For details, see text.

properties can be defined in simple terms as follows:

**2.5. Quality indicators** 

*Reliability* is the proportion (percentage) of right yes/no answers provided by independent tests for analyte identification in aliquots of the same sample in qualitative analyses.

*Representativenes*s is the degree of consistency of the results with the samples received by a laboratory, the overall sample or object studied, the particular analytical problem and the information required by the client.

*Basic analytical properties* (precision, robustness, sensibility selectivity) are attributes of analytical processes and provide support for capital properties. Thus, it is impossible to obtain highly accurate results if the analytical process is not precise, sensitive and selective enough. These properties can be defined as follows:

*Precision* is the degree of consistency among a set of results obtained by separately applying the same analytical method to individual aliquots of the same sample, the mean of the results constituting the reference for assessing deviations or random errors.

*Robustness* in an analytical method is the resistance to change in its results when applied to individual sample aliquots under slightly different experimental conditions.

*Sensitivity* is the ability of an analytical method to discriminate between samples containing a similar analyte concentration or, in other words, its ability to detect (qualitative analysis) or determine (quantitative analysis) small amounts of analyte in a sample.

*Selectivity* is the ability of an analytical method to produce qualitative or quantitative results exclusively dependent on the analytes present in the sample.

*Productivity-related properties* (expeditiousness, cost-effectiveness and personnel-related factors) are attributes of analytical processes with a very high practical relevance to most analytical problems.

*Expeditiousness* in an analytical method is its ability to rapidly develop the analytical process from raw sample to results. Expeditiousness is often expressed as the sample frequency (i.e. in samples per hour or per day).

*Cost-effectiveness* is the monetary cost of analyzing a sample with a given method and is commonly expressed as the price per analyte-sample pair. This property has two basic economic components, namely: the specific costs of using the required tools and the overhead costs of the laboratory performing the analyses.

*Personnel-related factors.* Strictly speaking, these are not analytical properties but are occasionally essential towards selecting an appropriate analytical method. These factors include the risks associated to the use of analytical tools and the analyst's safety and comfort.

As illustrated by Figure 6, quality in the results should go hand in hand with quality in the analytical process. In other words, capital analytical properties should rely on basic properties as their supports. It is a glaring error to deal with analytical properties in isolation as it has been usual for long. In fact, these properties are mutually related in ways that can be more consequential than the properties themselves. Their relationships are discussed in detail in Section 4. Each type of analytical problem has its own hierarchy of analytical properties, which materializes in the above-described "quality compromises".

Analytical Chemistry Today and Tomorrow 101

centuries and eventually become highly influential on human life and the environment by virtue of the increasing importance attached to social responsibility in Analytical Chemistry. "(Bio)chemical information" and "analytical information" are two equivalent terms in practice. In fact, the difference between chemical and biochemical analysis is irrelevant as it depends on the nature of the analyte (e.g. sodium or proteins), sample (e.g. soil or human

Information is the link between raw data and knowledge in the hierarchical sequence of Figure 7. *Primary* or *raw data* are direct informative components of objects and/or systems, whereas *information* materializes in a detailed description of facts following compilation and processing of data, and *knowledge* is the result of contextualizing and discussing information in order to understand and interpret facts with a view to making grounded, timely decisions. Einstein [9] has proposed *imagination* as an additional step for the sequence in critical situations requiring the traditional boundaries of knowledge to be broken by

**Figure 7.** "Information" as an intermediate step between "raw data" and "knowledge", and their

significance in the context of chemistry and biochemistry. For details, see text.

plasma) and tools involved (e.g. an organic reagent or immobilized enzymes).

**3.1. Contextualization** 

establishing new paradigms.

**Figure 6.** Holistic view of analytical properties as classified into three major groups and of their relationships with quality of the results and the analytical process. For details, see text.
