2 Modern Analytical Chemistry

1A What Is Analytical Chemistry?

“Analytical chemistry is what analytical chemists do.”*

We begin this section with a deceptively simple question. What is analytical chem-
istry? Like all fields of chemistry, analytical chemistry is too broad and active a disci-
pline for us to easily or completely define in an introductory textbook. Instead, we
will try to say a little about what analytical chemistry is, as well as a little about what
analytical chemistry is not.
Analytical chemistry is often described as the area of chemistry responsible for
characterizing the composition of matter, both qualitatively (what is present) and
quantitatively (how much is present). This description is misleading. After all, al-
most all chemists routinely make qualitative or quantitative measurements. The ar-
gument has been made that analytical chemistry is not a separate branch of chem-
istry, but simply the application of chemical knowledge.1 In fact, you probably have
performed quantitative and qualitative analyses in other chemistry courses. For ex-
ample, many introductory courses in chemistry include qualitative schemes for
identifying inorganic ions and quantitative analyses involving titrations.
Unfortunately, this description ignores the unique perspective that analytical
chemists bring to the study of chemistry. The craft of analytical chemistry is not in
performing a routine analysis on a routine sample (which is more appropriately
called chemical analysis), but in improving established methods, extending existing
methods to new types of samples, and developing new methods for measuring
chemical phenomena.2
Here’s one example of this distinction between analytical chemistry and chemi-
cal analysis. Mining engineers evaluate the economic feasibility of extracting an ore
by comparing the cost of removing the ore with the value of its contents. To esti-
mate its value they analyze a sample of the ore. The challenge of developing and val-
idating the method providing this information is the analytical chemist’s responsi-
bility. Once developed, the routine, daily application of the method becomes the
job of the chemical analyst.
Another distinction between analytical chemistry and chemical analysis is
that analytical chemists work to improve established methods. For example, sev-
eral factors complicate the quantitative analysis of Ni2+ in ores, including the
presence of a complex heterogeneous mixture of silicates and oxides, the low con-
centration of Ni2+ in ores, and the presence of other metals that may interfere in
the analysis. Figure 1.1 is a schematic outline of one standard method in use dur-
ing the late nineteenth century.3 After dissolving a sample of the ore in a mixture
of H2SO4 and HNO3, trace metals that interfere with the analysis, such as Pb2+,
Cu2+ and Fe3+, are removed by precipitation. Any cobalt and nickel in the sample
are reduced to Co and Ni, isolated by filtration and weighed (point A). After
dissolving the mixed solid, Co is isolated and weighed (point B). The amount
of nickel in the ore sample is determined from the difference in the masses at
points A and B.
mass point A – mass point B
%Ni = × 100
mass sample

*Attributed to C. N. Reilley (1925–1981) on receipt of the 1965 Fisher Award in Analytical Chemistry. Reilley, who was
a professor of chemistry at the University of North Carolina at Chapel Hill, was one of the most influential analytical
chemists of the last half of the twentieth century.
 Chapter 1 Introduction 3

Original Sample

1:3 H2SO4/HNO3 100°C (8–10 h)

dilute w/H2O, digest 2–4 h

PbSO4 Cu2+, Fe3+

Sand Co2+, Ni2+

dilute
bubble H2S(g)

Fe3+, Co2+, Ni2+ CuS

cool, add NH3

digest 50°–70°, 30 min

Fe(OH)3 Co2+, Ni2+

HCl slightly acidify w/ HCl

heat, bubble H2S (g)
Fe3+

neutralize w/ NH3 Waste CoS, NiS

Na2CO3, CH3COOH
aqua regia
heat, add HCl until
Basic strongly acidic
bubble H2S (g)
ferric
acetate

Co2+, Ni2+ CuS, PbS

heat
add Na2CO3 until alkaline
NaOH

Co(OH)2, Ni(OH)2 Waste

heat

CoO, NiO
Solid
heat, H2 (g)
Key
Solution
Co, Ni A

HNO3
K2CO3, KNO3
CH3COOH
digest 24 h

Ni2+ K3Co(NO3)5

H2O, HCl

Co2+ Waste

as above

Co B

Figure 1.1
Analytical scheme outlined by Fresenius3 for the gravimetric analysis of Ni in ores.
4 Modern Analytical Chemistry

Original sample

HNO3, HCl, heat

Residue Solution

20% NH4Cl
10% tartaric acid
take alkaline with 1:1 NH3
take acid with HCl
10% tartaric acid
take alkaline with 1:1 NH3 Is
Yes solid
present?

Solid
Key No
take acid with HCl
Solution 1% alcoholic DMG
take alkaline with 1:1 NH3

A Ni(DMG)2(s)
Figure 1.2
Analytical scheme outlined by Hillebrand and
Lundell4 for the gravimetric analysis of Ni in
ores (DMG = dimethylgloxime). The factor of
0.2031 in the equation for %Ni accounts for
mass A × 0.2031
the difference in the formula weights of %Ni = × 100
Ni(DMG)2 and Ni; see Chapter 8 for more g sample
details.

The combination of determining the mass of Ni2+ by difference, coupled with the
need for many reactions and filtrations makes this procedure both time-consuming
and difficult to perform accurately.
The development, in 1905, of dimethylgloxime (DMG), a reagent that selec-
tively precipitates Ni2+ and Pd2+, led to an improved analytical method for deter-
mining Ni2+ in ores.4 As shown in Figure 1.2, the mass of Ni2+ is measured directly,
requiring fewer manipulations and less time. By the 1970s, the standard method for
the analysis of Ni2+ in ores progressed from precipitating Ni(DMG) 2 to flame
atomic absorption spectrophotometry,5 resulting in an even more rapid analysis.
Current interest is directed toward using inductively coupled plasmas for determin-
ing trace metals in ores.
In summary, a more appropriate description of analytical chemistry is “. . . the
science of inventing and applying the concepts, principles, and . . . strategies for
measuring the characteristics of chemical systems and species.”6 Analytical chemists
typically operate at the extreme edges of analysis, extending and improving the abil-
ity of all chemists to make meaningful measurements on smaller samples, on more
complex samples, on shorter time scales, and on species present at lower concentra-
tions. Throughout its history, analytical chemistry has provided many of the tools
and methods necessary for research in the other four traditional areas of chemistry,
as well as fostering multidisciplinary research in, to name a few, medicinal chem-
istry, clinical chemistry, toxicology, forensic chemistry, material science, geochem-
istry, and environmental chemistry.
 Chapter 1 Introduction 5

You will come across numerous examples of qualitative and quantitative meth-
ods in this text, most of which are routine examples of chemical analysis. It is im-
portant to remember, however, that nonroutine problems prompted analytical
chemists to develop these methods. Whenever possible, we will try to place these
methods in their appropriate historical context. In addition, examples of current re-
search problems in analytical chemistry are scattered throughout the text.
The next time you are in the library, look through a recent issue of an analyti-
cally oriented journal, such as Analytical Chemistry. Focus on the titles and abstracts
of the research articles. Although you will not recognize all the terms and methods,
you will begin to answer for yourself the question “What is analytical chemistry”?

1B The Analytical Perspective

Having noted that each field of chemistry brings a unique perspective to the study
of chemistry, we now ask a second deceptively simple question. What is the “analyt-
ical perspective”? Many analytical chemists describe this perspective as an analytical
approach to solving problems.7 Although there are probably as many descriptions
of the analytical approach as there are analytical chemists, it is convenient for our
purposes to treat it as a five-step process:
1. Identify and define the problem.
2. Design the experimental procedure.
3. Conduct an experiment, and gather data.
4. Analyze the experimental data.
5. Propose a solution to the problem.
Figure 1.3 shows an outline of the analytical approach along with some im-
portant considerations at each step. Three general features of this approach de-
serve attention. First, steps 1 and 5 provide opportunities for analytical chemists
to collaborate with individuals outside the realm of analytical chemistry. In fact,
many problems on which analytical chemists work originate in other fields. Sec-
ond, the analytical approach is not linear, but incorporates a “feedback loop”
consisting of steps 2, 3, and 4, in which the outcome of one step may cause a
reevaluation of the other two steps. Finally, the solution to one problem often
suggests a new problem.
Analytical chemistry begins with a problem, examples of which include evalu-
ating the amount of dust and soil ingested by children as an indicator of environ-
mental exposure to particulate based pollutants, resolving contradictory evidence
regarding the toxicity of perfluoro polymers during combustion, or developing
rapid and sensitive detectors for chemical warfare agents.* At this point the analyti-
cal approach involves a collaboration between the analytical chemist and the indi-
viduals responsible for the problem. Together they decide what information is
needed. It is also necessary for the analytical chemist to understand how the prob-
lem relates to broader research goals. The type of information needed and the prob-
lem’s context are essential to designing an appropriate experimental procedure.
Designing an experimental procedure involves selecting an appropriate method
of analysis based on established criteria, such as accuracy, precision, sensitivity, and
detection limit; the urgency with which results are needed; the cost of a single analy-
sis; the number of samples to be analyzed; and the amount of sample available for

*These examples are taken from a series of articles, entitled the “Analytical Approach,” which has appeared as a regular
feature in the journal Analytical Chemistry since 1974.
6 Modern Analytical Chemistry

1. Identify the problem

Determine type of information needed 5. Propose a solution
(qualitative, quantitative,
Conduct external evaluation
characterization, or fundamental)

Identify context of the problem

2. Design the experimental procedure

Establish design criteria (accuracy, precision, 4. Analyze the experimental data
scale of operation, sensitivity, selectivity,
cost, speed) Reduce or transform data

Identify interferents Analyze statistics

Select method Verify results

Establish validation criteria Interpret results

Establish sampling strategy Feedback

loop

3. Conduct an experiment
Calibrate instruments and equipment

Standardize reagents
Figure 1.3
Gather data
Flow diagram for the analytical approach to
solving problems; modified after Atkinson.7c

analysis. Finding an appropriate balance between these parameters is frequently

complicated by their interdependence. For example, improving the precision of an
analysis may require a larger sample. Consideration is also given to collecting, stor-
ing, and preparing samples, and to whether chemical or physical interferences will
affect the analysis. Finally, a good experimental procedure may still yield useless in-
formation if there is no method for validating the results.
The most visible part of the analytical approach occurs in the laboratory. As
part of the validation process, appropriate chemical or physical standards are used
to calibrate any equipment being used and any solutions whose concentrations
must be known. The selected samples are then analyzed and the raw data recorded.
The raw data collected during the experiment are then analyzed. Frequently the
data must be reduced or transformed to a more readily analyzable form. A statistical
treatment of the data is used to evaluate the accuracy and precision of the analysis
and to validate the procedure. These results are compared with the criteria estab-
lished during the design of the experiment, and then the design is reconsidered, ad-
ditional experimental trials are run, or a solution to the problem is proposed. When
a solution is proposed, the results are subject to an external evaluation that may re-
sult in a new problem and the beginning of a new analytical cycle.
 Chapter 1 Introduction 7

As an exercise, let’s adapt this model of the analytical approach to a real prob-
lem. For our example, we will use the determination of the sources of airborne pol-
lutant particles. A description of the problem can be found in the following article:
“Tracing Aerosol Pollutants with Rare Earth Isotopes” by
Ondov, J. M.; Kelly, W. R. Anal. Chem. 1991, 63, 691A–697A.
Before continuing, take some time to read the article, locating the discussions per-
taining to each of the five steps outlined in Figure 1.3. In addition, consider the fol-
lowing questions:
1. What is the analytical problem?
2. What type of information is needed to solve the problem?
3. How will the solution to this problem be used?
4. What criteria were considered in designing the experimental procedure?
5. Were there any potential interferences that had to be eliminated? If so, how
were they treated?
6. Is there a plan for validating the experimental method?
7. How were the samples collected?
8. Is there evidence that steps 2, 3, and 4 of the analytical approach are repeated
more than once?
9. Was there a successful conclusion to the problem?
According to our model, the analytical approach begins with a problem. The
motivation for this research was to develop a method for monitoring the transport
of solid aerosol particulates following their release from a high-temperature com-
bustion source. Because these particulates contain significant concentrations of
toxic heavy metals and carcinogenic organic compounds, they represent a signifi-
cant environmental hazard.
An aerosol is a suspension of either a solid or a liquid in a gas. Fog, for exam-
ple, is a suspension of small liquid water droplets in air, and smoke is a suspension
of small solid particulates in combustion gases. In both cases the liquid or solid par-
ticulates must be small enough to remain suspended in the gas for an extended
time. Solid aerosol particulates, which are the focus of this problem, usually have
micrometer or submicrometer diameters. Over time, solid particulates settle out
from the gas, falling to the Earth’s surface as dry deposition.
Existing methods for monitoring the transport of gases were inadequate for
studying aerosols. To solve the problem, qualitative and quantitative information
were needed to determine the sources of pollutants and their net contribution to
the total dry deposition at a given location. Eventually the methods developed in
this study could be used to evaluate models that estimate the contributions of point
sources of pollution to the level of pollution at designated locations.
Following the movement of airborne pollutants requires a natural or artificial
tracer (a species specific to the source of the airborne pollutants) that can be exper-
imentally measured at sites distant from the source. Limitations placed on the
tracer, therefore, governed the design of the experimental procedure. These limita-
tions included cost, the need to detect small quantities of the tracer, and the ab-
sence of the tracer from other natural sources. In addition, aerosols are emitted
from high-temperature combustion sources that produce an abundance of very re-
active species. The tracer, therefore, had to be both thermally and chemically stable.
On the basis of these criteria, rare earth isotopes, such as those of Nd, were selected
as tracers. The choice of tracer, in turn, dictated the analytical method (thermal
ionization mass spectrometry, or TIMS) for measuring the isotopic abundances of
8 Modern Analytical Chemistry

Nd in samples. Unfortunately, mass spectrometry is not a selective technique. A

mass spectrum provides information about the abundance of ions with a given
mass. It cannot distinguish, however, between different ions with the same mass.
Consequently, the choice of TIMS required developing a procedure for separating
the tracer from the aerosol particulates.
Validating the final experimental protocol was accomplished by running a
model study in which 148Nd was released into the atmosphere from a 100-MW coal
utility boiler. Samples were collected at 13 locations, all of which were 20 km from
the source. Experimental results were compared with predictions determined by the
rate at which the tracer was released and the known dispersion of the emissions.
Finally, the development of this procedure did not occur in a single, linear pass
through the analytical approach. As research progressed, problems were encoun-
tered and modifications made, representing a cycle through steps 2, 3, and 4 of the
analytical approach.
Others have pointed out, with justification, that the analytical approach out-
lined here is not unique to analytical chemistry, but is common to any aspect of sci-
ence involving analysis.8 Here, again, it helps to distinguish between a chemical
analysis and analytical chemistry. For other analytically oriented scientists, such as
physical chemists and physical organic chemists, the primary emphasis is on the
problem, with the results of an analysis supporting larger research goals involving
fundamental studies of chemical or physical processes. The essence of analytical
chemistry, however, is in the second, third, and fourth steps of the analytical ap-
proach. Besides supporting broader research goals by developing and validating an-
alytical methods, these methods also define the type and quality of information
available to other research scientists. In some cases, the success of an analytical
method may even suggest new research problems.

1C Common Analytical Problems

In Section 1A we indicated that analytical chemistry is more than a collection of
qualitative and quantitative methods of analysis. Nevertheless, many problems on
which analytical chemists work ultimately involve either a qualitative or quantita-
tive measurement. Other problems may involve characterizing a sample’s chemical
or physical properties. Finally, many analytical chemists engage in fundamental
studies of analytical methods. In this section we briefly discuss each of these four
areas of analysis.
Many problems in analytical chemistry begin with the need to identify what is
qualitative analysis present in a sample. This is the scope of a qualitative analysis, examples of which
An analysis in which we determine the include identifying the products of a chemical reaction, screening an athlete’s urine
identity of the constituent species in a
for the presence of a performance-enhancing drug, or determining the spatial dis-
sample.
tribution of Pb on the surface of an airborne particulate. Much of the early work in
analytical chemistry involved the development of simple chemical tests to identify
the presence of inorganic ions and organic functional groups. The classical labora-
tory courses in inorganic and organic qualitative analysis,9 still taught at some
schools, are based on this work. Currently, most qualitative analyses use methods
such as infrared spectroscopy, nuclear magnetic resonance, and mass spectrometry.
These qualitative applications of identifying organic and inorganic compounds are
covered adequately elsewhere in the undergraduate curriculum and, so, will receive
no further consideration in this text.
 Chapter 1 Introduction 9

Perhaps the most common type of problem encountered in the analytical lab is
a quantitative analysis. Examples of typical quantitative analyses include the ele- quantitative analysis
mental analysis of a newly synthesized compound, measuring the concentration of An analysis in which we determine how
much of a constituent species is present
glucose in blood, or determining the difference between the bulk and surface con-
in a sample.
centrations of Cr in steel. Much of the analytical work in clinical, pharmaceutical,
environmental, and industrial labs involves developing new methods for determin-
ing the concentration of targeted species in complex samples. Most of the examples
in this text come from the area of quantitative analysis.
Another important area of analytical chemistry, which receives some attention
in this text, is the development of new methods for characterizing physical and
chemical properties. Determinations of chemical structure, equilibrium constants,
particle size, and surface structure are examples of a characterization analysis. characterization analysis
The purpose of a qualitative, quantitative, and characterization analysis is to An analysis in which we evaluate a
solve a problem associated with a sample. A fundamental analysis, on the other sample’s chemical or physical properties.
hand, is directed toward improving the experimental methods used in the other
areas of analytical chemistry. Extending and improving the theory on which a fundamental analysis
An analysis whose purpose is to improve
method is based, studying a method’s limitations, and designing new and modify- an analytical method’s capabilities.
ing old methods are examples of fundamental studies in analytical chemistry.

1D KEY TERMS
characterization analysis (p. 9) qualitative analysis (p. 8) quantitative analysis (p. 9)
fundamental analysis (p. 9)

1E SUMMARY
Analytical chemists work to improve the ability of all chemists to chemists to improve existing analytical methods and to develop
make meaningful measurements. Chemists working in medicinal new analytical techniques.
chemistry, clinical chemistry, forensic chemistry, and environ- Typical problems on which analytical chemists work include
mental chemistry, as well as the more traditional areas of chem- qualitative analyses (what is present?), quantitative analyses
istry, need better tools for analyzing materials. The need to work (how much is present?), characterization analyses (what are
with smaller quantities of material, with more complex materi- the material’s chemical and physical properties?), and funda-
als, with processes occurring on shorter time scales, and with mental analyses (how does this method work and how can it be
species present at lower concentrations challenges analytical improved?).

1F PROBLEMS
1. For each of the following problems indicate whether its d. The structure of a newly discovered virus needs to be
solution requires a qualitative, quantitative, characterization, determined.
or fundamental study. More than one type of analysis may be e. A new visual indicator is needed for an acid–base titration.
appropriate for some problems. f. A new law requires a method for evaluating whether
a. A hazardous-waste disposal site is believed to be leaking automobiles are emitting too much carbon monoxide.
contaminants into the local groundwater. 2. Read a recent article from the column “Analytical Approach,”
b. An art museum is concerned that a recent acquisition is a published in Analytical Chemistry, or an article assigned by
forgery. your instructor, and write an essay summarizing the nature of
c. A more reliable method is needed by airport security for the problem and how it was solved. As a guide, refer back to
detecting the presence of explosive materials in luggage. Figure 1.3 for one model of the analytical approach.
10 Modern Analytical Chemistry

1G SUGGESTED READINGS
The role of analytical chemistry within the broader discipline of Mottola, H. A. “The Interdisciplinary and Multidisciplinary
chemistry has been discussed by many prominent analytical Nature of Contemporary Analytical Chemistry and Its Core
chemists. Several notable examples follow. Components,” Anal. Chim. Acta 1991, 242, 1–3.
Baiulescu, G. E.; Patroescu, C.; Chalmers, R. A. Education and Tyson, J. Analysis: What Analytical Chemists Do. Royal Society of
Teaching in Analytical Chemistry. Ellis Horwood: Chichester, Chemistry: Cambridge, England, 1988.
1982. Several journals are dedicated to publishing broadly in the
Hieftje, G. M. “The Two Sides of Analytical Chemistry,” Anal. field of analytical chemistry, including Analytical Chemistry,
Chem. 1985, 57, 256A–267A. Analytica Chimica Acta, Analyst, and Talanta. Other journals, too
Kissinger, P. T. “Analytical Chemistry—What is It? Who Needs It? numerous to list, are dedicated to single areas of analytical
Why Teach It?” Trends Anal. Chem. 1992, 11, 54–57. chemistry.
Laitinen, H. A. “Analytical Chemistry in a Changing World,” Current research in the areas of quantitative analysis, qualitative
Anal. Chem. 1980, 52, 605A–609A. analysis, and characterization analysis are reviewed biannually
Laitinen, H. A. “History of Analytical Chemistry in the U.S.A.,” (odd-numbered years) in Analytical Chemistry’s “Application
Talanta 1989, 36, 1–9. Reviews.”
Laitinen, H. A.; Ewing, G. (eds). A History of Analytical Current research on fundamental developments in analytical
Chemistry. The Division of Analytical Chemistry of the chemistry are reviewed biannually (even-numbered years) in
American Chemical Society: Washington, D.C., 1972. Analytical Chemistry’s “Fundamental Reviews.”
McLafferty, F. W. “Analytical Chemistry: Historic and Modern,”
Acc. Chem. Res. 1990, 23, 63–64.

1H REFERENCES
1. Ravey, M. Spectroscopy 1990, 5(7), 11. 113–119; (c) Atkinson, G. F. J. Chem. Educ. 1982, 59, 201–202;
2. de Haseth, J. Spectroscopy 1990, 5(7), 11. (d) Pardue, H. L.; Woo, J. J. Chem. Educ. 1984, 61, 409–412;
(e) Guarnieri, M. J. Chem. Educ. 1988, 65, 201–203; (f) de Haseth, J.
3. Fresenius, C. R. A System of Instruction in Quantitative Chemical
Spectroscopy 1990, 5, 20–21; (g) Strobel, H. A. Am. Lab. 1990,
Analysis. John Wiley and Sons: New York, 1881.
October, 17–24.
4. Hillebrand, W. F.; Lundell, G. E. F. Applied Inorganic Analysis, John
8. Hieftje, G. M. Am. Lab. 1993, October, 53–61.
Wiley and Sons: New York, 1953.
9. See, for example, the following laboratory texts: (a) Sorum, C. H.;
5. Van Loon, J. C. Analytical Atomic Absorption Spectroscopy. Academic
Lagowski, J. J. Introduction to Semimicro Qualitative Analysis, 5th ed.
Press: New York, 1980.
Prentice-Hall: Englewood Cliffs, NJ, 1977.; (b) Shriner, R. L.; Fuson,
6. Murray, R. W. Anal. Chem. 1991, 63, 271A. R. C.; Curtin, D. Y. The Systematic Identification of Organic
7. For several different viewpoints see (a) Beilby, A. L. J. Chem. Educ. Compounds, 5th ed. John Wiley and Sons: New York, 1964.
1970, 47, 237–238; (b) Lucchesi, C. A. Am. Lab. 1980, October,