In the Classroom

Integration of Quality Assurance/Quality Control

into Quantitative Analysis
Suzanne C. Bell* and Jeff Moore
Department of Chemistry, Eastern Washington University, 526 Fifth Street, Cheney, WA 99004

Quality assurance/quality control (QA/QC) has become

paramount in industrial, government, and research laboratories. However, this vital aspect of chemistry is often peripherally discussed in chemistry curricula. The importance of
teaching these ideas is now being addressed (1). Quantitative
analysis (quant) offers the ideal venue to introduce QA/QC.
In this course, students can learn how QA/QC and statistics
are interpreted; how errors can be isolated; and how QA/QC is
used to troubleshoot and repair faulty procedures from inception through reporting. Furthermore, existing laboratories can
be modified to encompass QA/QC without implementation
of new exercises.
The goodness of analytical data is judged on the basis
of accuracy and precision. Quant unknowns are in a sense
unrealistic, since there is (usually) a true value associated with
that unknown. However, real samples do not have a known
value; the analyst must determine it, gauging reliability by
QA/QC data. Although traditional unknowns are essential
for evaluating student performance, it is equally essential that
students learn to interpret results when there is no known
standard. Numerous techniques can be employed. For example, students can estimate the accuracy of their analyses
using known samples provided to them. Precision can be gauged
through replicates. Coupling these to the analysis of blanks,
spikes (fortified samples), and traditional unknowns helps
students critique their own work while developing troubleshooting skills. Thus, QA/QC helps students develop invaluable analytical judgment.
Skills that emerge from the study and application of
QA/QC include problem identification and problem solving. In traditional courses, students turn in an unknown result with little, if any, sense of how they have done or whether
problems were encountered. QA/QC allows students to identify problems, study and optimize their techniques and procedures, and apply realistic uncertainties. Coupled to an understanding of statistics and underlying chemical principles,
QA/QC helps students to evaluate their work rather than
having a professor or teaching assistant (TA) tell them what
went wrong after it is too late to do anything about it. Such
postmortem feedback leads to unnecessary discouragement
and does not reflect analytical chemistry as practiced in most
laboratories outside academia.

limit, it is considered unacceptable (out of control) and

corrective measures must be taken.
Although the inclusion of a control chart exercise in quant
is laudable, it fosters the idea that QA/QC is a separate topic
rather than a continuing theme. Thus, the idea of a control
chart can and should be expanded. In quant for example,
students often perform iodometric titrations using thiosulfate,
a reagent subject to chemical and microbial degradation (4,
5). Control charting can be coupled with iodometric titrations as follows.
Students at Eastern Washington University (EWU) prepare
thiosulfate solutions without boiling the reagent water and
without pH control. Additionally, the solutions are stored in
sunlight. The solutions are initially standardized using 35
replicates. These data are used to generate the warning and
control limits, here defined as 1 and 2 standard deviation
units, respectively. Although more initial replicates would be
desirable, given time and reagent limitations, this represents
a reasonable compromise. Warning and control limits are
specified as 2 and 3 standard deviation units in Standard
Methods for the Examination of Water and Wastewater (6 ).
However, tighter limits are advantageous for several reasons.
Since standardization occurs early in the quarter, student technique (particularly reproducibility) is still improving; large
standard deviations (and thus large warning and control regions) often result. Under the quarter system, the time that

New Laboratory Exercises

A survey of the literature indicates that a preferred
method for integration of QA/QC into courses is through
control charts (2, 3). In such exercises, a simple analysis is
repeated throughout the term and the results are plotted. A
range of acceptable values is set, along with warning limits
and control limits that are also shown on the chart. Typically,
determination of the warning and control limits is based on
standard deviation. When a measured value exceeds a control
*Corresponding author.

874

Figure 1: Representative control charts. No Precautions indicates

that thiosulfate was made and stored without preservative steps.
The four lines are the upper and lower warning and control limits;
the x axis is molarity of the thiosulfate.

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In the Classroom

elapses from solution preparation to the final titration can

be as little as eight weeks. Thus, by narrowing the control
and warning limits, there is a greater chance these limits will
be crossed and students can discuss the implications.
After initial standardization, students titrate the
thiosulfate weekly using KI/KIO3 and plot the data. Representative control charts are shown in Figure 1. Note that the
control and warning limits for the upper chart, All Precautions
Taken, are larger than those for the lower chart. This is due
to the larger standard deviation of the replicates used to generate the former and reflects differences typically seen among
students. Interestingly, after running this laboratory for several quarters, many trends have been observed in addition to
the steady decline in concentration. These varying responses
could be due to improvement in titration technique, evaporative loss from the volumetric flask, some combination of
these factors, or others as yet undetermined. Over a semester
(several weeks longer than a quarter), clearer trends would
be expected.
Existing Laboratories
Laboratories constituting the backbone of traditional
quant courses (gravimetric, volumetric and electrochemical)
need not be discarded to include QA/QC. Consider the determination of the percent copper in a brass sample using a
thiosulfate/iodine titration:
1. A method blank is included in which all preparatory
steps are performed in the absence of brass.
2. A known sample is provided; students perform a single
titration and calculate their results. The percent error
between the experimental and true value is calculated
and students decide whether further practice is needed
before unknowns are attempted. Within the constraints
of time and reagent supply, students are allowed to
repeat the known titration as many times as they wish.

Addition of these two QA/QC samples helps students detect

systematic errors such as impure reagents, errors in calculations,
and contaminated glassware. Thus, they can proceed to the
unknown with confidence in their technique and reagents.
3. Replicates of the unknown (n = 3) are added. This
affords students a measure of precision and is used to
calculate a percent relative standard deviation (%RSD,
the standard deviation divided by the mean and multiplied by 100) and a confidence interval (95%) for
their result.

Target values for percent errors on knowns and for

%RSD are based on the technique and performance of past
classes. Students are graded on accuracy (gauged by their
known and unknown) and precision (gauged by %RSD).
Using all QA/QC data (blank, known, and replicates), students
identify systematic errors, postulate sources, offer solutions, and
predict the impact on their unknown results. For example,
assume a student performed the titrations described above.
The blank showed residual copper or other reactive components,
the known showed a positive error, and the replicates generated
a %RSD of 1%. The student would be expected to predict
good precision but a high bias on the unknown results due
to a systematic error traceable to contamination. This is a
classic example of precise but inaccurate results, easily associated with target analogies used in many textbooks (4, 5).

Use of Spikes and Fortified Samples

Blanks, replicates, and knowns suffer from the limitation that they are separate from the actual unknown sample.
Thus, analytical problems arising from the matrix (such as
masking, adsorption) escape detection. This problem has been
addressed using internal standard calibration, standard addition,
and fortification (spiking) of samples. Two types of spikes are
commonly used, matrix spikes and surrogate spikes. Consider
the analysis of mouthwash for fluorine using an ion-selective
electrode. Students calibrate the electrode using an aqueous
solution of NaF, and both knowns and unknowns using this
matrix typically work well, assuming ionic strengths are kept
constant. However, it is not unusual for the results of a
mouthwash analysis to differ significantly from the label value.
Students investigate potential sources of the error using a
matrix spike sample.
Students take a sample of mouthwash that does not
contain fluoride and add a known amount of F to the matrix
such that the concentration falls in the middle of the calibrated
range. The percent recovery of spiked fluorine provides the
students with the data required to distinguish a matrix problem from problems related to uncertainty in the label value
and calculations. Coupled with other QA/QC results (blanks,
knowns, and replicates), the students can discuss the reliability
of their analysis with confidence.
Surrogate spikes are another type of QA/QC geared toward identification of matrix effects or other problems
associated with a specific sample. Surrogates are elements or
compounds that are chemically related to the target analyte
but are not likely to be found in the sample. By determining
the percent recovery of the surrogate, the analyst can estimate the reliability of the result obtained for the target analyte. Use of surrogates requires multielement or multicomponent capability such as afforded by gas chromatography
(GC). In addition, organic analyses are well suited for surrogate spikes since compounds similar to the analyte are readily
available and by definition, amenable to the same chromatographic conditions as the target analyte. Fluorinated or deuterated compounds are a good choice for surrogates when
using GC and GC coupled to mass spectrometry (GCMS)
because these compounds are rarely found in natural matrices such as soil and water.
At EWU, students analyze swimming pool water for
chloroform that forms as a by-product of chlorination. Purgeand-trap (PT) preconcentration is used, coupled to GCMS,
and an Environmental Protection Agency (EPA) method format is followed. The instruments and experimental conditions are summarized in the box. Students are responsible for
sample collection based on EPA protocols. They collect two
sets of samples; the first with no headspace in the vial, the
second allowing large amounts of headspace. Prior to the laboratory, the instructor performs the MS tuning and initial calibration. When students arrive, they are responsible for the
tune check, calibration check, and loading of all samples up
to the autosampler capacity of 16. With group sizes typically
34, each student has the chance to load multiple samples.
This loading procedure includes addition of surrogate and
internal standards to each sample using microsyringes. Because pool water rarely imparts a matrix effect, students include a synthetic sea water sample in their batch to simulate

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In the Classroom
Instruments and Experimental Conditions
Instrument

Hewlett-Packard 6890 GCMSD

Column and temperature

program

HP-624, 25.0 m 200 m 1.12 m;

35 C for 2 min, then 6/min to 180 C

Purge-and-Trap

Hewlett-Packard Purge and Trap

concentrator with 16-position heated
autosampler unit

Trap and conditions

Software

Vocarb 3000; 11-min purge time, 40

mL/min, desorb for 2 min at 225 C
HP EnviroQuant, Rev. C

Sample size

5.0 mL

Standards

internal: ,,-trifluorotoluene, 50.0 ppb

surrogate: 4-bromofluorobenzene,
50.0 ppb

potential matrix interferences, which should be reflected in

poor recovery of the surrogate standard.
After samples are loaded, students complete the sequence
table in the GCMS software that controls operations including analysis, quantitation, and reporting. The sequence
is started and samples are run overnight, yielding several pages
of quantitative data, QA/QC data, and calibration information.
Since the pool samples are not prepared by the instructor or
TA, there is no way to know a true value and no way to
calculate a percent error based on student results. Therefore,
students rely on QA/QC to evaluate their data.
Typical student results (five student groups) are presented
in Table 1. Note that pool water samples were collected over
several days; the concentration of chloroform was not constant.
Variation among student groups is clearly evident, and in
some cases, the concentration of chloroform in the vial with
headspace was found to be higher than in vials without headspace. Surrogate recoveries were also low. Variations were attributed to the students inexperience with microsyringes. The
poor reproducibility likely resulted from different students
loading the individual samples.
The goal here was not so much perfection of the technique as exposure to EPA-type analyses and the accompanying blizzard of information (analytical and other) that results.
While the volume of data can be daunting, it is an accurate
reflection of commercial analytical data reduction. Thus, this

876

laboratory provides an ideal capstone laboratory which integrates laboratory, instrument, QA/QC, and data analysis
skills. Other laboratories such as those involving spectrophotometry and high pressure liquid chromatography can be
modified into similar capstone exercises. Since the instrument
has to be calibrated for one sample the same as for a dozen,
such laboratories are time and cost-effective.
Other Procedures
QA/QC is not limited to the bench. Rather, it encompasses the analytical process from sample collection through data
reporting. Appreciation for this cradle-to-grave philosophy
of QA/QC can also be addressed in quant, again, with modest
alteration of existing procedures. At EWU, students use
spreadsheets for data analysis, statistics, and calibration curves.
As part of QA/QC, they verify formulas used in the spreadsheets and document this in their laboratory notebook. An
appreciation for calibration is covered in the discussion of
calibration of analytical balances using certified weights. Calibration check standards obtained from commercial sources
are used to verify calibrations and students are required to
document all relevant information, including lot numbers and
expiration dates. Thus, the concept of traceability is stressed
in lectures and reinforced in the laboratory.
Much QA/QC is either directly related to or included in
the laboratory notebook. Traditional instruction for keeping
this vital document has been relegated to a few pages in most
texts. However, given the current litigious climate and recent
scandals surrounding notebook documentation, it is crucial
that students learn to keep a legally defensible notebook at
the earliest opportunity. For many, this opportunity is quant.
In the EWU course, provisions for notebooks are stringent.
A partial list of requirements includes:

All pages, front and back, must be signed and dated

with a full legal signature
Black or blue ink is required.
Typed procedures (reduced copies) are pasted or taped
in the notebook, with initials through at least two
points separating the inserted paper and the notebook
page. This way, if material is ever removed, the initials will be partially removed as well and the removal
will be immediately obvious.

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In the Classroom

Sources of all data, information, and reagents must be

completely documented.
Copies of all spreadsheets, graphs, and final reports
must be included.
Blank pages must be either marked through or explained;
e.g, The next ten pages are left blank for spacing.
Any corrections made must be indicated by a single
line through the discarded sections. Furthermore, the
student must initial any mark-throughs and briefly explain why the data was discarded.
Serial numbers plus complete descriptions (make,
model, etc.) of all instrumentation are required.
Any computer documents included must be clearly
identified by name, date, and file name.
The ten-year rule applies: The information in the
notebook must be complete enough that the entire experiment could be duplicated without any ambiguity
ten years hence.

Initially, students struggle with the format; after that the

rigorous procedures become habit. The best student notebooks are used as examples for later classes. More importantly,
these notebooks can demonstrate to potential employers that
the student is capable of generating defensible documentation.
Like an understanding of QA/QC, this is a valuable and transportable skill that will serve students long after they have left
the Chemistry Department.
Time Management and Other Considerations
The above procedures, with some variations, have been
in use at EWU since late 1994. Several students have received
jobs or internships in which they reported that the course
format was especially helpful. These include positions with
local environmental laboratories, forensic laboratories, and
pharmaceutical companies. In comments on the course students
typically report that although it was more work than expected,
they appreciated the attention to technical writing, details of
laboratory technique, and especially the skills obtained with
spreadsheets and word processors. However, redesign of the
course required careful planning and a continually evolving,
flexible approach.
One of the limitations with integration of QA/QC is
the added time and effort involved. This is a tradeoff made
in commercial laboratories as well, seeking a balance between
reasonable and appropriate QA/QC versus the time and effort
required to generate it. However, a balance is found and QA/
QC has become ubiquitous, the purpose being to insure the
goodness of analytical results. Thus, inclusion of QA/QC in
quant, a course geared toward teaching measurement science,
should not be a question of if but rather how. In turn,
how requires a thoughtful assessment of resources, class size,
and curricular concerns. Typically, students require more
hands-on guidance with this approach in the earlier weeks
of the term. In turn, this requires additional laboratory management and supervision by the instructors and experienced
TAs to insure success. More reagents are needed and larger
quantities of waste are generated. All these factors need to be
weighed, but the main issue is the additional time needed to
complete labs when QA/QC samples are added.
The amount of additional time required varies depending on the procedure. In general, laboratories utilizing

a calibration curve are least impacted. Consider again the

analysis of mouthwash for fluoride using an ion selective
electrode. The bulk of the laboratory time is devoted to
preparation of calibration standards. Adding a blank, known,
matrix spike, and replicate unknowns still allows for completion of the exercise, including preparation of a calibration
curve and analysis of a calibration check solution, in a single
3-hour laboratory period. On the other hand, the determination of copper in brass by a redox titration as mentioned above
typically takes 56 laboratory hours from initial preparations
through reagent standardization, analysis of blanks, knowns,
and 3 replicates of the unknowns. This compares with an
estimated 34 hours when QA/QC samples are not included.
To offset additional time requirements, several approaches
are taken, not the least of which is teaching students to work
efficiently. The framework of the course is such that students
are essentially free to organize their time. Reagents are made
well in advance, and instrument access is scheduled early in
the quarter. Moreover, students are not allowed to work outside
the scheduled laboratory hours, even to wash glassware. Given
the large number of laboratories required (1114) and the
inflexible and regular due dates (12 reports per week), students
quickly become adept at allocating their time. Interestingly,
this includes arriving prepared for the work ahead rather than
reading a laboratory for the first time the same day they plan
to do it. With time rationed, they learn how wasteful this
practice is.
In addition, students quickly realize that good results on
the known predict good accuracy on the unknown, which
in turn represents a large proportion of their grade. It is not
unusual to find students doing additional replicates of the
knowns, testing the purity of reagents, or doing additional
replicates of the unknown rather than leaving 15 minutes
early. Thus, the design of the course is such that students are
motivated to learn time management and to exploit the value
of QA/QC within the context of inflexible deadlines and
limited samples and reagents. In the workplace, no less will
be expected of them.
Acknowledgments
Suzanne Bell is grateful to the National Science Foundation (ILI grant 95-51724) and to several sections of quant
students who patiently and with enthusiasm performed and
critiqued the cited experiments. Jeff Moore, who did his portion of this work while an undergraduate at EWU, is now
employed with Bayer Corporation, Pharmaceutical Division,
Analytical Quality Assurance Laboratory, Spokane, WA.
Literature Cited
1. Perone, S. P.; Englert, P.; Pesek, J.; Stone, C. J. Chem. Educ. 1993,
70, 847.
2. Marcos, J.; Rios, A.; Valcarcel, M.; J. Chem. Educ. 1995, 72, 947.
3. Laquer, F. C.; J. Chem. Educ. 1990, 67, 900.
4. Skoog, D. A.; West, D. M.; Holler, F. J.; Analytical Chemistry: An
Introduction, 6th ed.; Saunders: Philadelphia, 1994.
5. Harris, D. Quantitative Chemical Analysis, 4th ed.; Freeman: New
York, 1995.
6. Standard Methods for the Examination of Water and Wastewater,
19th ed.; Eaton, A. D.; Clesceri, L. S.; Greenberg, A. E., Eds.;
EPA Group: Hanover, MD, 1995; Section 1-6.

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