Trends in Analytical Chemistry 114 (2019) 98e107

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Trends in Analytical Chemistry

journal homepage: www.elsevier.com/locate/trac

Analytical reliability of simple, rapid, minuturizated, direct analytical

processes: A call to arms

María Laura Soriano a, b, c, Mohammed Zougagh a, b, c, Angel rcel d, e, *
Ríos a, b, Miguel Valca
a
Regional Institute for Applied Chemistry Research (IRICA), 13004 Ciudad Real, Spain
b
Department of Analytical Chemistry and Food Technology, University of Castilla e La Mancha, 13071 Ciudad Real, Spain
c
Department of Analytical Chemistry and Food Technology, Faculty of Pharmacy, University of Castilla e La Mancha, 02071 Albacete, Spain
d
Spanish Royal Academy of Sciences, Valverde 24, E-28071 Madrid, Spain
e rdoba, E-14071 Co
Faculty of Sciences, University of Co rdoba, Spain

a r t i c l e i n f o a b s t r a c t

Article history: There is an urgent need to assure the quality of the results provided by rapid, simple and direct analytical
Available online 12 March 2019 processes, ordinary not involving sample preparation steps. These analytical systems, sometimes called
“tests methods”, which are of increasing importance in the production of data, information and
Keywords: knowledge, are outlined here. To support this goal, an analytical property named “reliability”, non-
Analytical chemistry systematically used, is fully defined here by emphasizing its summative character of the other analyt-
Reliability
ical properties, as well as by exploiting the fact that its meaning is well understood by the society. After
Quality assurance
describing the principal bottle-necks of analytical chemistry, the relationships between clients and
Test methods
End-users
analysts, as well as the types of analytical results are discussed. In the second part, the basic definition
Satisfaction allows to show the variety of meanings of it. Then, analytical reliability is fully described by showing the
application the adjective reliable in this context, as well as the way that it can express almost homo-
geneous reliability of test methods providing different analytical results. These aspects are proposed and
discussed in this review.
© 2019 Elsevier B.V. All rights reserved.

1. Introduction decisions. In fact, timely decisions in societal areas (medical, agri-

In a recent paper, Whitesides [1] warned that the current role of
analytical chemistry is “more important than it seems”, because
this discipline should be concerned mainly with the extraction of
reliable (bio)chemical information from objects and systems. It
must substantially contribute solve real problems of human activ-
ities, as well as to produce the reinvention of Chemistry in partic-
ular and Science in general, opening new areas of science. It is hard
to imagine progress in society, science and technology without
reliable information or knowledge of static and dynamic objects.
However, many scientists, technicians and politicians are unaware
of the strategic significance of new instruments and sensors to
societal needs, genuine innovation and the emergence of new
research avenues. As conceded by Whitesides, this lack of aware-
ness is a serious bottleneck for progress and the source of wrong
 rdoba, E-14071
* Corresponding author. Faculty of Sciences, University of Co
rdoba, Spain.
Co
E-mail address: qa1vacam@uco.es (M. Valc
arcel).
food, industrial, etc.) and science and technology can hardly be
made without reliable information or knowledge. Many scientific
studies in fields such as proteomics, genomics or metabolomics, for
example, have failed to adopt systematic analytical quality assur-
ance, which raises the question as to how results can possibly be
made reliable simply by sequentially analyzing two aliquots of the
same sample with an automatic system that processes hundreds if
not thousands of samples on a daily basis.
These problems are of great importance if the analytical device
is simple, rapid, automated, miniaturized [2] and used out of the
laboratory by non-experts (on-site [3]). Thus, the main aim of this
article is to promote quality assurance of these increasingly
important analytical devices and the corresponding results by
using a simple property. This property is the compilation of the
classical ones, and it is easy to be understood by non-specialists,
thus facilitating the friendly relationships between analysts and
“clients”, asking/receiving the analytical information or knowledge
[4]. It is as urgent issue, which is a bottle-neck in analytical
chemistry. A mobilization (“call to arms”) is necessary.

https://doi.org/10.1016/j.trac.2019.03.005
0165-9936/© 2019 Elsevier B.V. All rights reserved.
 M.L. Soriano et al. / Trends in Analytical Chemistry 114 (2019) 98e107
2. Main bottle-necks in analytical chemistry
A rigorous examination of reality and foreseeable trends in
analytical chemistry allows outlining relevant constrictions/limi-
tations for achieving the main goals of this chemical discipline [5],
which are commented on below.
(a) Instruments and sensing systems always provide data. To
assure that measured primary data unequivocally corre-
sponds to the reality is a crucial challenge for analytical
chemists.
(b) Scarce participation of analytical chemist after providing the
primary data. They should be very active in the sequence
primary data-information (results) e knowledge (reports)
[4]. The role of analytical chemists in the production of in-
formation and knowledge should be recognized by other
professionals.
(c) Looking for publication rather than usefulness of approaches
for solving analytical problems [6]. This is a common draw-
back in many areas of today's science and technology. As
asked Ioannidis [7] in the clinical field, it is possible to ask in
our realm: “Why the majority of Analytical Chemistry research is
not useful?” Satisfaction of demands of (bio)chemical infor-
mation should substitute number of papers, journal impact
factors, Hirsh index, etc., as targets. Such is the case of the
development of certified reference materials (CRM), which is
an important hole in analytical chemistry because only 5e7%
of needs for validating analytical processes are covered. This
topic is considered of second or third class by editors of highly
reputed journals, as well as for the national and international
bodies promoting and funding R&D activities.
(d) Scarce true innovation in analytical research that should be
far from repetitions with small changes with the assurance
that the research will finish in a paper without interest. True
innovation should involve assuming risk of failure, breaking
the mental and inter-areas frontiers, creating new para-
digms, fostering imagination and creativity, among other
meanings [6].
(e) Lack of harmonization between basic and applied analytical
chemistry as consequence of the previous bottle-neck. The
publication of articles should not be the end of a venture of
analytical research. This is a consequence of the wrong
assessment of scientists, research groups and centers: the
qualitative evaluation should have a similar importance as
regards the conventional quantitative.
(f) The reduced importance of transfer of knowledge and tech-
nology in analytical research groups or Centers. This is a
great error which needs to be urgently corrected because the
consolidation of our discipline depends on this activity. This
activity should be well recognized in the scientific and
technical assessment.
(g) Little tendency to work in an interdisciplinary context. The
future of chemistry [8] and analytical chemistry [9] is to work
with other scientists and professionals. This will be the way
to support an efficient transfer of analytical science and
technology.
(h) Scarce interest in the social consequences of the analytical
activities and the impact of the analytical results provided.
Social Responsibility should be an essential issue in analyt-
ical chemistry [10].
(i) Wrong approach to education in analytical chemistry based
mainly on the description of ionic equilibria and classical and
instrumental methods/techniques. Teaching analytical
chemistry should start describing its foundations [5] before
constructing the so named “analytical knowledge building”.
99
(k) The misunderstanding between what is the validation of a
method and what are its performance characteristics. Simply,
validation involves performance characteristics plus fitness
for purpose. From this binomial, it can be distinguished two
main objectives: (i) Method development, generally in the
research domain and the corresponding publication in sci-
entific journals. Here, the characterization of the method
predominates with respect to fitness for purpose: it is pro-
posed the method for same specific application(s), but with a
reduced number of samples and, normally, applied in a short
period of time. (ii) Method application in control/routine
laboratories, working in many cases under accreditation
framework following the norm ISO 17025. Accreditation
bodies require a systematic validation of the selected method,
as well as the corresponding internal and external quality
control activities (control charts and participation in profi-
ciency testing rounds, respectively) [11]. This double approach
is clear and reasonable, and also necessary because it is the
difference between R&D and routine (accredited) use of the
analytical methods. And it is the reality, because research
groups do not use analytical methods daily in a routine way,
whereas routine laboratories normally do not develop new
analytical methods but use existing ones.
The right strategies of the present and future of analytical
chemistry should take into account all these bottle-necks, in order
to address the efforts to circumvent them.
3. The relationships between analytical chemists and
“clients”
Analytical chemistry is what analytical chemists do, and the
activities of analytical chemists deal with three main goals: (i) to
develop the basic aspects of the discipline (R&D þ i activities),
where “clients” are the scientific community and society in general;
(ii) to implement the applied aspects through the (bio)chemical
analysis, and here “client” is society in the most wide dimension;
and (iii) education and dissemination activities where “client” are
the students and people who like science. Each purpose has
different nuances, but in most cases the activity of analytical
chemists is associated to the implementation of chemical analysis,
where the information generated wants to be used to solve
particular problems of the society in general and the physical
person(s) in particular. How are the relationships between the
analytical chemists and the end users of the analytical information?
These relationships must be established at different hierarchical
levels, as it is illustrated in Fig. 1.
Although the final goal is making decisions for problem solving,
and hence the need for consistency between the required and
delivered analytical information [12], the rational steps to take go
from the inside to the outside of laboratory. Thus, the first task
consists in the selection of the analytical process and to plan the
corresponding sampling protocol, and then the implementation
from a practical point of view. In this analytical chain connecting
results with the system objective of the information, it is necessary
to establish an accurate relationship between the laboratory sam-
ples and the corresponding results (traceable results with the cor-
responding uncertainties, from a metrological point of view) [13].
The use of robustness methods has a positive influence in the
comparability between laboratories, very important from a prac-
tical point of view for the end users, and clear objective of the
accreditation programs. But, even more important, it involves the
appropriated sampling plans to assure the representativeness of
the results with respect the physical-chemical system [14]. Here,
the well-defined analytical problem, thanks to the scientific-
100 M.L. Soriano et al. / Trends in Analytical Chemistry 114 (2019) 98e107

Fig. 1. Different hierarchical levels between analytical information and the client information needs.

technical understanding between the analytical chemist and the
client, makes possible to define and characterize the system under
study from an analytical point of view according to the client
information needs [15]. Reliability, in the analytical field [16], as
discussed later on, must be associated to the final elaborated in-
formation delivered to the “client”, and its consistency to solve
specific real problems.
4. Types of analytical results
The expansion of analytical chemistry has propitiated the
amplification of the types of analytical results, as is shown in the
central part of Fig. 2. In fact, according to Heydorn [17] a measurand
is the “quantity intended to be measured”. The measurand is the
objective of the information (qualitative and/or quantitative), and
different types of results can be associated to this information.
Nowadays, other analytical measurands are widely used as conse-
quence of the simple, rapid, miniaturized, automated, on-site, etc.
analytical measurement processes. Some of these results are
commented on below.
4.1. Quantitative results
They are typical numbers or figures that reflex the concentration
or absolute amount of an analyte in a particular sample. The appli-
cation of quality assurance principles and practices allows to express
these quantitative results with an uncertainty interval at a fixed level
of probability (e.g., 3.34 ± 0.03 mg/g with an uncertainty expressed
as expanded uncertainty at k ¼ 2, approximately 95% confidence
level). In analytical field, traceability must be demonstrated [18] and
uncertainty estimated [19], taken into account the peculiarities of
metrology applied to chemical-analytical measurements [20].
4.2. Qualitative results
Qualitative results have traditionally been associated to the
identification of chemical substances. However, qualitative analysis
was considered as an obsolete analytical field (e.g., Fresenius
scheme) in the second half of XX century. But the view of the
chemical qualitative information importantly changed at the
beginning of XXI century due to two main factors: (i) the growing

Fig. 2. Types of analytical measurands and their relationships with classical metrology and new analytical technologies to satisfy the client's information needs.
 M.L. Soriano et al. / Trends in Analytical Chemistry 114 (2019) 98e107
need to identify more and more compounds in numerous fields of
application, together the greater amount of qualitative information
provided by the current analytical instrumentation (increasingly
sophisticated); and (ii) the increasing recommendations (even from
the EU) that control laboratories adopt screening methods for a
rapid classification of samples as positive or negative according to
levels established by legislation or by the client. The “MEQUALAN”
EU Project was an important support to disseminate this new view
of qualitative analysis, including interesting conclusions [21].
Additionally, it was the subject matter of a special issue of TrAC in
2005 [22].
For modern qualitative analysis associated to the identification
of compounds, is worthy to remark the contributions of Milman,
collected in a book in 2011 [23]. In this facet of qualitative analysis
two different approaches are distinguishes today: target identifi-
cation (does the analyte present in the sample?); and non-target/
unknown identification (what analyte present in the sample?). In
both cases, the problem can be the availability of pure substances
which can be used as references. The way to express the results is
the “match factor” (in percent to coincide with the reference takes
for the identification, commonly). The principal approaches used
for identification purposes are: (i) co-analysis (simultaneous anal-
ysis with an authentic reference material, which is the best alter-
native if possible); (ii) comparison to experimental reference data
(spectral libraries and databases); (iii) comparison to theoretical/
predicted reference data (e.g., retention index in GC, simulation of
NMR spectra, or prediction of mass spectra); and (iv) data inter-
pretation from data (spectra) using special rules and algorithms
(this is the principal approach in structure elucidation of new
compounds). In all these cases, the basis of identification is based
on the statistical match factors.
When qualitative analysis is addressed to the classification of
the samples, they are expressed as binary YES/NO responses. They
are the simplest approach to classification analysis in chemo-
metrics realm [24]. In this case, the peculiar analytical properties
[25] including reliability [25] and uncertainty [27] have been
published. The fact that accuracy, precision and uncertainty cannot
be applied in this context allows developing non-orthodox
metrological approaches to be adapted to its peculiarities [20].
4.3. Total or global indices
These indices can be defined as measurands that describes a
group of (bio)chemical compounds that have [28]: (i) similar (bio)
chemical nature/structure (e.g., polychlorinated biphenyls (PCBs),
fats, polyphenols); and/or (ii) similar operational behavior (e.g.,
pollutants, toxics, adulterants, endocrine disrupters). The potential
group of compounds can range from millions (e.g., total hydrocar-
bons in soil) to a few ones (e.g., total mercury in sea water). These
compounds can be of the same chemical structure (e.g., total pol-
yaromatic hydrocarbons, PAHs) or different (e.g., contaminants that
contribute to chemical oxygen demand, COD; species that act as
antioxidants in foods, etc.). This type of information is increasingly
required by clients. A bottle-neck of these chemical parameters is
the lack of tangible metrological standards for calibration and
method validation.
4.4. Method-defined parameter
It can be defined as a measurand that can be obtained only by
using a well-established and detailed (bio)chemical measurement
process, which has been designed to fulfill a well-defined purpose
when dealing with a specific type of sample in a particular field [29]
(e.g., “hexane extractable material”, “bitterness in beer”, “chemical
oxygen demand”, “leachable metals in ceramics”, etc.). In this case,
101
tangible measurement standards are not involved in calibration
and validation procedures, but the well-defined method is
considered as a standard by itself. Quality should be assured by
interlaboratory exercises using the same methodology. But, previ-
ously, for a rigorous and accepted use, the corresponding method
must be evaluated by means of a collaborative exercise in order to
produce a standard accepted method by the accreditation bodies.
4.5. Brief discussion on the type of analytical results
As can be seen in Fig. 2, the maximum level of metrological
support corresponds to Quantitative Analysis. It is easy to adapt to
quantitative results the metrological principles and practices,
mainly originally devoted to physical measurements. But this
classical metrological support is progressively loosed when the
analytical process produce binary and total indices responses, pa-
rameters defined by a specific method, etc., that are the measur-
ands produced by new simple, rapid on-site analytical
methodologies. Thus, the main aim of this article is to guaranty the
quality of these new measurands/analytical information by using
an unusual analytical property as it is reliability.
In the last steps of the central sequence in Fig. 2 (total indices,
method-defined parameters) in which the classical metrological
approach is minimized, it is mandatory to exploit the concept of
“consensus standard”: a heterodox metrological standard that is
universally accepted by all the partners involved in a specific fields
of interest. Such is the case of the “bitterness of beers” total index,
which based on the absorbance of an extract at 275 nm multiplied
by an empirical factor of 50 by a well-defined method. This
approach allows one to establish a universal scale of bitterness of
beers. It is interesting to note that this index can be also considered
a method-defined parameter because the method applied should
be strictly the same.
5. On-site, simple, direct, automated, miniaturized, portable,
cheaper, greener analytical processes
There is a clear tendency in analytical chemistry to develop new
analytical processes with these and other productivity character-
istics because the demands of (bio)chemical information to make
sound, fast decisions have been dramatically changed. All the ad-
jectives of the title are interrelated (e.g., an analytical process could
be simple, on-site, disposable, miniaturized, cheaper, rapid, etc.).
Almost all of them imply the minimization or avoidance of sample
preparation procedures in analytical processes. A schematic view of
all of these properties associated to such terms is shown in Fig. 3.
An impressive number of home-made or commercially-
available analytical devices have been developed in the last de-
cades in many fields of human activities (e.g., Clinical, Pharmacy,
Industrial, Foods, Agriculture, Nanotechnology, etc.). All of them
need a rigorous quality assurance approach although they are
generally used without any metrological support. Such is the case
of the well-known proteomics analysis. Some of them are: minia-
turized systems [2], point-of-care tests [30], laboratory-developed
tests [31], portable instruments [32], on-site and in-vivo devices
[33], strip-tests [34] in the context of the so named “dry chemistry”
[35], disposal analytical systems [36] among many others. They are
used billons of times a day all over the world. All of glucometers, the
diabetes patients do not used a standard, which is commercially
available, but difficult to find out in the drugstores for sale. The
literature in this context is not easy because the abundance of ar-
ticles or reports from commercial vendors without a sound, basic
description of these analytical devices.
These systems produce easily fast results not well metrological
supported. Ordinarily, they are the output of the so called “sample
102 M.L. Soriano et al. / Trends in Analytical Chemistry 114 (2019) 98e107

Fig. 3. Network of interrelated characteristics of modern fast and direct analytical processes (tests).

screening systems” [37] in the context of the so named “vanguard-
rearguard analytical strategies” [38] to confirm/validate the “easy
results”.
6. Reliability in analytical chemistry
Fig. 4 depicts a multifaceted approach to “reliability” (“the
quality or state of being reliable”). According to reputed English
dictionaries [39,40], the adjective “reliable” is equivalent to
“trustworthy”, “confident”, “safe”, “sure”, “transparent”, “qualified”
or “socially responsible”, among other meanings. It is, thus, an in-
tegral or cumulative concept, very rich in confluent meanings, and
with application in every area or social context. It is interesting to
emphasize that the meaning of reliability is directly related with
the metrological realm according to its definitions in English
dictionaries, which is an argument that also supports this article. To
be reliable in Metrology is expressed in the three definitions
depicted in Fig. 4 that can be condensed in two statements:
reproducibility of measurement procedures, and production of
satisfactory results close to the reality they try to describe. Reli-
ability is a term very easily understood by scientists, analysts and
citizens alike. Thus, it is a key in human/institutional relationships
as well as a property that globally facilitates the mutual relation-
ships between “clients” demanding information and analytical
laboratories.
6.1. Definition and relationship with other analytical properties
Analytical reliability can be defined as a property to characterize
the consistency of the analytical information in terms of quality and

Fig. 4. Compilation of the variety of general and metrological meanings of the adjective “reliable” in Oxford [39] and Webster [40] English Dictionaries.
 M.L. Soriano et al. / Trends in Analytical Chemistry 114 (2019) 98e107
usefulness for end-users. It is a cumulative highest level property
associated to the whole analytical levels of coherence already
showed in Fig. 1. It involves the quality of the results, the analytical
processes, the sampling protocols; but also the appropriate defi-
nition of analytical problem in order to produce usefulness infor-
mation for the client. Globalize and fully represents the total of
classical analytical properties [5], namely: the top ones (accuracy,
representativeness), the basic ones (precision, robustness, selec-
tivity, sensitivity) and the productive ones (rapidity, low cost, low
risks). Reliability is, thus, a summative property, which facilitates
the two-way relationships between analytical chemists and clients,
because of its general meaning is well understood by society.
It is of particular interest for modern, fast and simple analytical
processes implementing sample screening [37], because they pro-
duce easily data from analytical processes managed by non-skilled
people, which urgently need a friendly approach to assure and
express analytical quality. It is interesting to note that the word
“test” is included among the metrological definitions of English
dictionaries (see Fig. 4). Another subsidiary meaning of the word
reliability, although more secondary, deals with its “vocation” to act
as an interface between different relevant aspects of the analytical
discipline Reliability can be considered the link between: (i)
method development and true validation of the method because
the proper development connect with the true fitness for purpose
of method validation implemented in laboratories; (ii) basic and
applied research owing to meaning of usefulness of the general
definition of analytical reliability; (iii) top/basic analytical proper-
ties and the productive ones as it is explained below and graphi-
cally shown in Fig. 5.
Thus, in 1993, a systematic and hierarchical classification was
proposed by establishing thee groups of analytical properties [41],
namely: (i) top analytical properties (accuracy and representative-
ness), that are attributes to the analytical results, and can be
considered partially their reliability; (ii) basic analytical properties
(robustness, precision, sensitivity and selectivity), attributed to the
analytical process which are the support of the top ones (e.g.,
accuracy cannot be achieved without precision or selectivity); and
finally (iii) productive analytical properties (simplicity, rapidity,
costs, risks), which also are characteristics of analytical processes.
These last properties, same times called “complementary” prop-
erties, are essential in fast, simple, direct analytical processes, the
target of this paper, as well as to other analytical methods. As it is
Fig. 5. Links between reliability and classical analytical properties. For details, see text.
103
shown in Fig. 5, reliability is a summative analytical property which
encompasses the three types of classical analytical properties. This
is one of its main added value. As it was reported previously [41],
the competitiveness of the analytical information is achieved by
adopting quality compromises between the top/basic analytical
properties supporting the quality, and the productive ones. This is
only a partial contradiction between competitiveness of the
analytical information and reliability of the analytical information.
The answer to the question “is it reliable?” does not be a binary
response yes/no. It depends on the usefulness of the information
for the client in order to solve its particular problem at right time.
As in the control quality charts, warning and action limits should be
associate to analytical reliability. But it is clear that, the information
given by a laboratory in the emergency service of a hospital must be
given as soon as possible, but within the accepted reliability, in
order to be useful for the doctor and the patient.
According to Wenclawiak [42] the adjective “reliable” can be
applied to different essential aspects in analytical chemistry. Thus,
following this author: (i) an analytical laboratory that can achieve
reliability with the accomplishment of basic steps starting with the
implementation of a Quality Management System, followed by the
Certification of it; (ii) analytical process implemented in the labo-
ratory, the reliability of which is achieved via accreditation by a
national independent and reputed organization; (iii) analytical tools
involved in analytical process (e.g., sampling devices, solvents and
solid-phase extractors, measurement systems, etc.), the quality of
which should be assured to assign individually the adjective “reli-
able”; and (iv) analytical results provided by analytical processes, the
reliability of which is based on the reliability of the analytical pro-
cesses and the tools provided and the reliability of the laboratory.
Accepting reliability is a common word of general use, in our
opinion the use of analytical reliability should be limited to the
overall analytical information as discussed before. There are
another well-coined terms referred to the well-done/quality of the
other aspects: analytical laboratory with certification/accreditation;
analytical process with validation; analytical tools with calibration;
and analytical results with accuracy and representativeness.
Another important concern is the possible misunderstanding
between unreliability and validation by analytical professionals.
This problem comes from a non-appropriate understanding of the
real meaning of validation from a practical point of view. Thus, it is
very common to see in the analytical publications a section on the
104 M.L. Soriano et al. / Trends in Analytical Chemistry 114 (2019) 98e107
validation of the method, when in fact it is an analytical charac-
terization of the method. For the true validation of the method, two
possible metrological ways can be followed: (i) external validation
through a collaborative exercise managed by a recognized body, in
order to produce standardized methods; (ii) the internal validation
of a particular method by a laboratory following the established
schemes by accreditation bodies or other recognized bodies. In all
cases, a deeper examination and testing of the method will be
performed, in contrast to the simple analytical characterization for
the publication in a scientific journal. In this context, it is very
interesting the discussion reported in a recent article published by
Rudaz and Feinberg [43]. However, the measurement uncertainty
cannot be considered as the ‘ultimate’ criterion for accepting the
reliability of an analytical method as the authors stated. Although
the importance of the uncertainty and the tolerance intervals,
traceability and the fitness for purpose (connexion to the client/
end-user) are more important criteria.
6.2. How to express analytical reliability?
The consolidation of reliability as summative property strongly
depends on the existence of indicators/markers of it applied to the
results. Probably the absence of them is the reason why reliability
has not widely used, although its strategic importance. The
contribution detailed here is, of course, open to be completed/
modified. It is based on basic approaches to chemometrics and
metrology in chemistry. It is possible that there are other similar
approaches in the literature but not related to reliability. A general
approach is not possible, because depends on the type of results,
but it is necessary to look for a minimum homogeneity in its
expression. Thus, we propose a relative expression of reliability,
that is, as percentage or proportion in all types of analytical results,
as explained below. In consistence con the definition given for
reliability in Section 6.1, the percentage must include aspects
associated to the quality of the information, and aspects associated
to the usefulness of it for end-users (client).
6.2.1. Reliability in qualitative analysis
This term already exists in this type of information as the pro-
portion (%) of correct YES/NO responses when n aliquots of the
same sample are subjected to the same qualitative analytical pro-
cess, frequently named as “test” or “sample screening system” or
“vanguard analytical system”:
Reliability ð%Þ ¼ 100  % false responses ðnegative and positive responsesÞ
where k is a numerical factor (from 1 to 10) that reflects the
importance of the false negative or positive responses in different
contexts. For instance, in clinical field “false positives” are of critical
importance, and this factor should be high owing to the social
relevance to avoid false negatives. The ideal situation is to achieve
100% of reliability or a 0% of “false negatives”. For a k ¼ 5, and a 2% of
false negatives (%Reliability ¼ 100  5  2 ¼ 90%) is worse than and
overall reliability of 85%, with a 0% of false negatives. On the con-
trary, “false positives” are critical for the export of agricultural
products, where the level of pesticide residues is controlled. In this
case, the opposite consideration can be stated.
It is curious to state that it is not possible to establish a metro-
logical uncertainty interval to the binary YES/NO response as un-
certainty in quantitative results. To solve this problem, in the
MEQUALAN EU project [21] and some related reference [44] a new
parameter was proposed: the unreliability interval, that it can be
defined as de concentration or quantity interval around the
threshold limit, where the errors are produced at a fixed probability
level. In Fig. 6B as is shown a schematic differentiation between
both ranges in qualitative and quantitative analysis. It is interesting
to note that the unreliability interval is the opposite of the concept
of reliability, the topic of this article.
6.2.2. Reliability in quantitative analysis
Although it is common to speak about the reliability of a
quantitative method, it is more an evaluative term than a quanti-
tative one. In this case, it is necessary to introduce some approach
to establish some reliability parameter analogous to this use in
qualitative analysis. Again, the two components of the definition of
reliability must be taken into account: quality and user needs.
Validation is the key activity to connect with these objectives. Thus,
in terms of quality, after the demonstration of traceability of the
method, the bias associated to this method are a clear quality
parameter; whereas in terms of client requirements the uncer-
tainty/tolerance of the provided information can be useful for this
purpose. Therefore, in this case it is possible to establish reliability
in the following terms:
Reliability ð%Þ ¼ 100  Bias ð%Þ  Uncertainty ð%Þ
where uncertainty is expressed as expanded uncertainty. The
involved percentages in this equation are calculated by:

 
 
This general and simple expression is associated to quality as- Rexp  Rref 
pects, but the interest of the client (“end-user”) establishes the
Bias ð%Þ ¼  100
Rref
importance of negative or positive false responses according to a
preset threshold. Therefore, a more dedicated expression will be
needed as follows:

Reliability ð%Þ ¼ 100  k$% false responses ðonly negative or positive responsesÞ
 M.L. Soriano et al. / Trends in Analytical Chemistry 114 (2019) 98e107
Fig. 6. Reliability in qualitative analysis and the comparison to uncertainty in quantitative results.
where R refers to results (experimental, Rexp, or the reference result
for the validation of the method in terms of traceability, Rref). And
for uncertainty term:
Uexp
U ð%Þ ¼  100
Uclient
Here, again, Uexp is the declared expanded uncertainty for the
method after the validation, and Uclient is the uncertainty/tolerance
established by the client (in the wider sense of the term, as the
client can be also represented by the legislation).
6.2.3. Reliability of total indices
Total indices methods are a particular case of quantitative
methods. The importance of total indices [26] arises from two facts.
On the one hand, they are often produced by test methods, and on
the other hand they represent about the 70% of the real-non arti-
ficially invented-requirements of (bio)chemical information. There
are two main types of total indices depending on their measure-
ment origin: (i) they can be based on a common signal to which
each compound of the group contributes in different degree to the
parameter; and (ii) they are based on adding-up, ratio, equation,
etc. of the contributed signal for each compound.
Method calibration is a weakness of the processes providing
total indices results because of the lack of proper standards to
support metrological quality. It is necessary to adapt (or to invent)
reliable approaches for a non-pure metrological calibration. In this
context, there are three types of methods according to the adapted
standards involved. In all these cases, reliability (%) can be
expressed by the general equation of quantitative methods, with
some particularities:
(i) Standardless methods without tangible measurement stan-
dards, as gravimetric methods widely used to provide total
indices (i.e., total solids in vinegar, total carbon in organic
products, or total dietary fiber in foods). These are in fact
calculable-absolute methods very close to physical mea-
surements, where traceability is directly associated to the
calibration of the analytical balance with certified weights.
Bias and uncertainty are basically very small, and they can be
105
associated to those of the proper values of balance
calibration.
(ii) Methods based on a single standard that is a representative
pure substance of the group commercially available as
reference material (RM). It is used to establish the conven-
tional calibration curve of relative methods (i.e., the use of
pure phenol as RM to provide the phenol index, the signal
provided by the mixture of phenols is related to the con-
centration of phenol). This is a heterodox approach to
metrology, but strictly necessary in (bio)chemical measure-
ments. Reliability in these cases can follow the general
equation. On the other hand, there are many titrimetric
methods that provide total indices (i.e., total acidity in wa-
ters, total proteins in animal feed, reducing substances in
molasses, etc.). In this case, the standard involved (i.e., po-
tassium phthalate in the determination of total acidity con-
tent of wines) does not contain any of the substances than
can be present in the target group. In this case, the analytical
method corresponds to a calculable method with general
chemical standards. Traceability is associated to both the
calibration of the burette and the standardization of the
titrant reagent with a primary standard.
(iii) Methods based in a mixture of standards, trying to be repre-
sentative of the mixture of chemicals that contributed to the
total index. The standard should be well-defined and accepted
by consensus. If it is proposed by a reputed organization (i.e.,
IUPAC), both conditions are fulfilled. For example, the use of
the calibration graph for the determination of total hydro-
carbon index of a well-defined standard mixture of linear and
cyclic alkanes and aromatic compounds. This standard
mixture is a commercially available RM. These are empirical
methods which can follow the general equation for reliability
as that of quantitative methods.
6.2.4. Reliability in method-defined parameters
These parameters are produced by a detailed and specific
method [29]. The detailed protocol of it acts as the standard itself. If
the method is different, the parameter is undefined (e.g., using
106 M.L. Soriano et al. / Trends in Analytical Chemistry 114 (2019) 98e107
different leaching solutions based on acetate and EDTA to extract
potassium in soils). Many of them are produced by test methods
and, thus, the reliability of which is very significate from a practical
point of view (i.e., total hydrocarbon in soils, hexane extractable
material in all types of water, corrosively towards steel, etc.). Many
of them also are total indices.
To express reliability (%) of well-defined methods producing
parameters, the reference should be the method itself and the
quality procedure should be the validation of the method involving
an interlaboratory approach (collaborative study) using the same
sample, that was previously prepared and fully characterized by the
leader laboratory. Ordinarily, these parameters are quantitative
results, where the main lack of reliability is associated to the
collaborative/interlaboratory study, which is the critical point to
assure the traceability. In this case, bias and uncertainty will be
characterized by relatively high values.
7. Final remarks
The use of reliability as a property in analytical chemistry is
scarce, probably due that this characteristic cannot be found in
metrological or chemical dictionaries, although general ones rec-
ognizes that the adjective reliable can be applied to “tests”. Many
analytical publications describe complex analytical processes
without a true validation. This negative tendency is based on the
use of almost false real (e.g., spiked) or “easy” (e.g., tap water)
samples, although there are coherent and justified applications
involving easy matrices. This is not the correct way that implies the
use of real samples (e.g., CRM). Usefulness [6] of the proposed
analytical processes is an essential aspect frequently forgotten by
analytical researchers. The use of reliability will reinforce useful-
ness of new test methods.
The purpose of this article is to show to analytical community
and “clients” expecting (bio)chemical information, the advantage of
the use of reliability as a cumulative or global propriety that can
facilitate understanding and avoid doubts and misunderstandings
with a particular focus on simple, rapid systems providing atypical
results. The most relevant contribution of it is the proposal of the
way to express reliability when the analytical process offers qual-
itative and quantitative conventional results, total indices and
method-defined parameters.
Finally, the authors recommend to introduce reliability studies in
the first part of the analytical method validation processes, because
the great added value of this property to characterize an analytical
method, in particular addressed to the fitness for purpose of the
methods and, thus, the connection to the client requirements and the
real world. This parameter summarizes very well, and in a simple way
without any complicate statistics calculation, the intrinsic quality of
the method in coherence with the usefulness and intended uses.
Acknowledgements
The Spanish Ministry of Economy and Competitiveness
(MINECO) and JJCC Castilla-La Mancha are gratefully acknowledged
for funding this work with Grants CTQ2016-78793-P and SBPLY/17/
180501/000262, respectively. M.L. Soriano also thanks the Euro-
pean Commission and the JJCC Castilla-La Mancha for the funding
project SBPLY/17/180501/000333.
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