Analytical Science Defined
As you navigate your local grocery store, you ponder the accuracy of product labels, starting with a jar of peanut butter that states it contains 190 mg of sodium per serving This curiosity continues as you examine toothpaste, which lists a fluoride content of 0.15% weight per volume Your intrigue deepens when you reach the pharmaceutical section and discover a vitamin bottle claiming 1.7 mg of riboflavin per tablet Each label prompts you to question how manufacturers determine these precise measurements.
Everyday experiences, such as shopping at a grocery or hardware store, reveal the importance of understanding product compositions, from cleaning fluids to fertilizers Many people have engaged in similar tasks at home, like monitoring ammonia levels in aquariums or testing water quality with kits for pH and hardness This hands-on experience may lead to the realization that such analyses are straightforward However, the complexity of scientific methods becomes apparent when considering how forensic scientists identify DNA on crime scenes or how researchers measure ammonia levels on Jupiter and ozone concentrations over the North Pole, showcasing the advanced techniques used in environmental and forensic science.
Analytical science is the field focused on identifying and quantifying the components of material systems through a process known as analysis, which can include both physical and chemical methods When chemical processes are involved, it is referred to as chemical analysis or analytical chemistry In this context, substances like sodium in peanut butter, nitrate in water, and ozone in the air are termed analytes, while the material containing the analyte is called the matrix Additionally, the term "assay" is used when an analysis is conducted to determine the concentration of a specific named substance within a material, such as measuring the percentage of aspirin in a bottle labeled "aspirin."
L1519_Frame_C01.fm Page 1 Monday, November 3, 2003 11:27 AM www.pdfgrip.com
2 Analytical Chemistry for Technicians assay for aspirin In contrast, an analysis of the aspirin would imply the determination of other minor ingredients in addition to the aspirin itself.
The purpose of this book is to discuss in a systematic way the techniques, methods, equipment, and processes of this important, all-encompassing science.
Classifications of Analysis
Analytical procedures can be categorized based on their objectives and methods, specifically into qualitative and quantitative analyses Qualitative analysis focuses on identifying the presence of substances without measuring their quantities, such as detecting mercury in lake water without reporting its amount In contrast, quantitative analysis determines the exact amounts of known components within a sample, like measuring potassium levels in garden soil at 342 parts per million (ppm) This article primarily emphasizes quantitative analysis, while also addressing some qualitative applications for specific techniques.
Analysis procedures can be categorized into three main types: those based on physical properties, wet chemical analysis, and instrumental chemical analysis Physical property analysis does not involve chemical reactions and often employs straightforward, sometimes computerized, devices for measurement This method is particularly effective for identification purposes and can also be applied to quantitative analysis when properties like specific gravity or refractive index change with the concentration of an analyte in a mixture.
Wet chemical analysis encompasses traditional methods that rely on chemical reactions and stoichiometry, utilizing only basic equipment like weighing devices These classical techniques have been employed in analytical laboratories for many years, predating the advent of electronic instruments When performed correctly, wet chemical analysis offers a high level of accuracy and precision, although it typically requires more time to complete.
Characterizing a material involves both qualitative and quantitative analysis, providing a comprehensive overview of its properties and the identity and quantity of its components For instance, a perfume manufacturer may describe its product by detailing its fragrance, longevity, and skin feel, alongside disclosing the specific ingredients and their amounts This characterization extends to the raw materials, the final product, and even the packaging, playing a crucial role in ensuring product quality throughout the manufacturing process.
Instrumental analysis employs advanced electronic instrumentation and high-tech techniques, often integrating complex hardware and software Although it may not always match the precision of traditional wet chemical methods, it offers faster analysis and broader applicability This approach is particularly effective for identifying minor constituents or trace elements in samples, rather than focusing on the major components.
We discuss wet chemical methods in Chapters 3 and 5 Chapter 15 is concerned with physical properties;Chapters 7 to 14 involve specific instrumental methods.
The Sample
In the context of material analysis, the term "bulk system" refers to the entire substance being examined For instance, when analyzing toothpaste for fluoride content, the bulk system encompasses the toothpaste within the tube Similarly, when assessing ammonia levels in aquarium water, the bulk system includes all the water present in the aquarium.
Analyzing bulk systems in an analytical laboratory often requires a practical approach, as it is not feasible to examine the entire system directly For instance, bringing all the soil samples into the lab for analysis is impractical.
In the chemical process industries, both qualitative and quantitative analyses are essential for evaluating various company products and their raw materials Qualitative tests often involve mixing a test sample with a reagent to observe a color change, which can be used to verify the contents of materials such as tribasic calcium phosphate, a key raw ingredient in certain pharmaceutical products.
The test sample is dissolved in water, acidified, and then tested with a molybdate solution A yel- low precipitate indicates that the material is indeed tribasic calcium phosphate.
Eric Niedergeses inspects a test tube for a yellow precipitate to verify that the drum's contents are tribasic calcium phosphate, while additional test tubes from other drums are organized in a rack on the bench before him.
In analytical chemistry, technicians collect representative samples from various sources, such as soil from a garden or water from a lake, to determine specific chemical content, like phosphate or mercury These samples, which must accurately reflect the characteristics of the entire bulk system, are then analyzed in the laboratory to identify or quantify the analytes present, such as sodium in peanut butter The rigorous laboratory operations performed by technicians ensure precise results that are essential for understanding the composition of the original material.
To ensure accurate analysis, the sample collected must be representative of the entire system, reflecting its true characteristics The process of collecting and preparing samples is crucial, and we will delve into this topic in detail in Chapter 2.
The Analytical Strategy
The determination of an analyte’s identity or concentration in a laboratory involves multiple steps, which can be organized into major parts for a coherent understanding These steps may differ based on the specific analyte, its matrix, and the chosen analytical methods This section introduces a general organizational framework, referred to as the analytical strategy, which will be further developed in subsequent chapters focusing on each major analysis method.
The analytical strategy consists of five key components: obtaining the sample, preparing the sample, conducting the analysis method, processing the data, and calculating and reporting the results These steps are visually represented in the flow chart in Figure 1.1 While the terminology and procedures outlined may be unfamiliar at this stage, they will be thoroughly explained in the upcoming chapters.
Analytical Technique and Skills
Manufacturers ensure the accuracy of nutritional labels, such as the 22 g of carbohydrates in a serving of Cheerios TM, through rigorous testing and quality control processes They conduct precise measurements and analyses to confirm that the stated amounts are correct, preventing discrepancies like labeling it as 20 g or 25 g Similarly, for products like rubbing alcohol, manufacturers utilize standardized testing methods to verify the concentration of isopropyl alcohol, ensuring the label's claim of 70% is accurate and reliable.
The percentage of 65% or 75% relates to the quality of the manufacturing process and the precision of measurement by the companies' quality assurance laboratories, significantly influenced by the expertise of the technicians conducting the analyses.
An analytical laboratory technician is an individual with a unique mindset and specialized skills, characterized by meticulous attention to detail and a steadfast commitment to obtaining high-quality data and results This role demands strong analytical techniques and skills, ensuring that even the simplest laboratory tasks are executed with precision and care.
Quality is paramount in analysis due to the significant implications of the results Careful handling of samples and materials in the lab is essential, as any contamination or loss through preventable accidents is unacceptable The outcomes of chemical analyses can have serious consequences, influencing critical decisions such as a prisoner's freedom, potential financial losses for industrial companies, or even the life and death of hospital patients.
Students need to cultivate a mindset conducive to effective practices in an analytical laboratory It is essential to pause and consider potential risks before advancing to the next procedural step, as this can prevent contamination or sample loss For instance, when stirring a solution in a beaker, one must carefully evaluate the implications of removing the stirring rod before proceeding to the subsequent steps.
Analytical science involves careful techniques to ensure accuracy in measurements, such as rinsing any liquid that clings to a rod back into a beaker upon removal This practice is crucial to avoid losing any portion of the solution, as even minor losses can lead to significant errors in analytical determinations.
The quality of techniques in analytical laboratories is crucial, leading to the establishment of laws known as Good Laboratory Practices (GLPs) by Congress in the late 1980s These regulations focus on essential aspects such as proper labeling, meticulous record-keeping, effective storage, and thorough documentation of laboratory procedures, referred to as Standard Operating Procedures (SOPs), as well as formal laboratory protocols.
FIGURE 1.1 Flow chart of the analytical strategy.
To prepare a sample for analysis, it is essential to weigh or measure its volume and perform specific physical or chemical processes, including drying and dissolving.
Obtain Weight or Volume Data on the Prepared Sample.
… Some methods involve simple weight loss or gain In other cases, a sample weight or volume is needed to calculate results.
Prepare Reference Standards of the Analyte or Substances with Which the Analyte Will React.
… One or more such solutions may be needed to calibrate equipment or to otherwise compare to or react with the analyte in the sample.
Standardize Solutions or Calibrate Equipment.
To accurately analyze a sample, it is essential to have known quantities for comparison, such as solutions that react with the analyte or calibration constants derived from these known values Additionally, the analyte may need to be physically or chemically separated from the sample matrix to ensure precise results.
Obtain the Required Data for the Sample.
… This is the final critical piece to most analysis methods.
This requires calculations and/or the plotting of a calibration curve from which the desired results can be derived Statistics are usually involved.
A final calculation may be necessary to obtain the desired results.
The sample must be representative of the bulk system; its integrity must be maintained; and the chain of custody must be documented.
Carry Out the Analysis Method
Calculate and Report the Results
Analytical chemistry for technicians is guided by written documents that outline laboratory operations, including authority over work aspects and the procedures for modifying Standard Operating Procedures (SOPs) Good Laboratory Practices (GLPs) facilitate regular audits by external personnel to ensure regulatory compliance, highlighting their significance in analytical laboratories For more details, refer to Appendix 1.
ACHEM Inc., based in Cleburne, Texas, specializes in producing high-purity bulk chemicals tailored for industries with stringent purity requirements To ensure product quality, rigorous quality assurance operations are conducted to detect trace levels of contaminants, as even minimal contamination can significantly impact results Consequently, laboratory activities are performed in a controlled environment known as a clean room, where strict protocols are implemented to prevent contamination Personnel are equipped with specialized clean room suits, hair nets, and protective gear, including gloves and safety glasses, to maintain the integrity of the chemical processing environment.
SACHEM produces tetramethylammonium hydroxide (TMAH) for the semiconductor industry, where suspended particles in TMAH solutions can lead to significant mechanical damage to electronic devices To ensure product quality, accurately determining particle content in these solutions is essential This process utilizes a laser-equipped particle counter, achieving a 70% detection efficiency Additionally, counting must occur in a clean room environment to prevent airborne particles from contaminating the solutions and skewing results.
To meet the required environmental standards, the concentration of airborne particles measuring 0.5 mm or larger must not exceed 1000 per cubic foot Generally, customers specify that TMAH solutions should contain fewer than 100 particles per milliliter for particles of the same size or greater.
Paul Plumb from SACHEM Inc utilizes a laser-equipped particle counter to measure particles in ultrapure TMAH solutions within a clean room environment, ensuring precision and contamination control, as indicated by his use of a hair net and specialized lab coat.
The Laboratory Notebook
Effective record keeping is a crucial aspect of Good Laboratory Practice (GLP) regulations, as it serves as a legal document Maintaining accurate and thorough records is essential for high-quality analytical science, requiring careful attention to the integrity and purpose of the data collected for samples and analytes.
Accordingly, an analytical laboratory will usually have strict guidelines with respect to laboratory notebooks The following typifies what these guidelines might be:
Every notebook should start with a table of contents, ensuring all pages are numbered and these numbers are accurately reflected in the table It is essential to keep the table of contents updated as projects are finalized and new ones are initiated.
B All notebook entries will be made in ink Use of graphite pencils or another erasable writing instrument is strictly prohibited.
No data entries should be erased or rendered illegible In the event of an error, simply draw a single line through the incorrect entry; do not use correction fluid Always initial and date any corrections, clearly indicating the reason for the change.
The notebook must remain in the laboratory at all times, except when recording data at remote locations or if special permission is obtained from the supervisor.
"The Paper Chase," a 1973 film, follows a student's journey to obtain a law degree at a prestigious Ivy League university The film features John Hausman as the formidable Professor Kingsfield, known for his intimidating presence and high expectations in the classroom His character instills fear in students through demanding hard work and precise answers This is exemplified during the first class when he enters with a commanding presence, declaring, “You come into my classroom with a skull full of mush, but you will leave thinking like a lawyer,” setting the tone for the rigorous academic challenges ahead.
This law school is renowned for producing exceptional lawyers, a reputation acknowledged by Professor Kingsfield, who emphasizes a serious approach in his class He insists on precision and attention to detail from the outset, setting high standards for his students.
Mastering analytical chemistry skills is crucial, as a well-equipped analytical laboratory demands precision and clarity of thought Developing strong laboratory techniques is essential for achieving success in the field and ensuring the overall success of a company's objectives.
A professor of analytical chemistry might say: “You come into my laboratory with a skull full of mush, but you will leave thinking like an analytical chemist.”
For each project undertaken, it is essential to maintain a consistent notebook format that includes the following components: **_title and date_**, a purpose or objective statement, data entries, results, and conclusions Each of these elements plays a crucial role in documenting the project's progress and outcomes.
“objective,” “data,” etc., to clearly identify the beginning of each section.
When documenting a project, ensure that notebook entries are made on consecutive pages whenever possible Start each new project on the front side of a fresh page, and only skip pages if necessary to adhere to this guideline.
G Draw a single diagonal line through blank spaces that consist of four or more lines (including any pages skipped according to guideline F above) These spaces should be initialed and dated.
H Never use a highlighter in a notebook.
I Each notebook page must be signed, dated, and possibly witnessed.
All new experiments should start with the title of the work and the date of execution If the experiment is resumed on a different date, it is essential to note that date at the point of continuation.
B The title will reflect the nature of the work or shall be the title given to the project by the study director.
III Purpose or objectives statement
A Following the title and date, a statement of the purpose or objective of the work will be written. This statement should be brief and to the point.
B If appropriate, the SOPs will be referenced in this statement
When performing work, it is essential to enter data directly into the notebook, as the use of loose pieces of paper for intermediate recordings is not allowed All entries must be made in ink to ensure clarity and permanence.
Any deviations from the Standard Operating Procedures (SOPs) must receive prior approval from the study director, and it is essential to document these deviations comprehensively, specifying the nature of the deviation and the reasons behind its occurrence.
Detailed descriptions of the analyzed samples are essential This includes information about the sample's source, the procedures followed to ensure representativeness (referencing standard operating procedures if applicable), and any special coding assigned to the samples along with their meanings Additionally, if codes were documented in a separate notebook, such as a field notebook, it is important to cross-reference this notebook for accuracy.
D Show the mathematical formulas utilized for all calculations and also a sample calculation.
E Construct data tables whenever useful and appropriate.
F Both numerical data and important observations should be recorded.
Limit attachments such as chart recordings and computer printouts to one per page, using clear tape or glue for adherence; avoid staples Only one fold in attachments is permitted, and ensure that no notebook entries are obscured by these attachments.
The project's results, including numerical analysis values, should be presented in table format when suitable If tables are not applicable, a concise statement of the outcomes should be provided In cases where a single numerical value represents the result, it should be clearly reported To determine what results to include, it is essential to consider the client's specific needs and expectations.
A After results are reported, the experiment is drawn to a close with a brief concluding statement indicating whether the objective was achieved.
Errors, Statistics, and Statistical Control
Errors
Errors in the analytical laboratory are basically of two types: determinate errors and indeterminate errors.
Determinate errors, or systematic errors, are identifiable inaccuracies that occur during laboratory work, often due to avoidable factors such as contamination, improperly calibrated instruments, reagent impurities, equipment malfunctions, poor sampling techniques, or calculation mistakes When laboratory results are affected by these known errors, they must either be discarded or, in cases of calculation errors, recalculated to ensure accuracy.
Determinate errors, also known as biases, stem from unavoidable sources and occur consistently every time a procedure is performed While these errors are known to happen, their predictable nature allows for the application of correction factors to mitigate their impact.
FIGURE 1.2 Sample pages from a laboratory notebook that a student is using for Experiment 6 in this text.
Indeterminate errors, or random errors, are unpredictable and cannot be specifically identified, making them unavoidable in measurements Unlike determinate errors, which can be recognized and corrected, the impact of indeterminate errors on results cannot be immediately dismissed or compensated for Instead, statistical analysis is necessary to assess whether the results deviate significantly from expected values.
“off-track” to merit rejection.
Statistics define the quality thresholds for results obtained from specific methods A laboratory result is deemed "acceptable" if it falls within these established limits To grasp how these thresholds are determined and to identify unacceptable results, a fundamental understanding of statistics is essential This article provides a concise overview of basic statistical concepts.
Elementary Statistics
To assess the acceptability of a result, identical tests are repeatedly conducted on the same sample using the same equipment This process reveals indeterminate errors, which are reflected in values that vary positively and negatively from the average of all obtained values Understanding these concepts is essential for grasping fundamental statistical terms.
1 Mean In the case in which a given measurement on a sample is repeated a number of times, the average of all measurements is called the mean It is calculated by adding together the numerical values of all measurements and dividing this sum by the number of measurements In this text, we give the mean the symbol m The true mean, or the mean of an infinite number of measure- ments (the entire population of measurements), is given the symbol m, the Greek letter mu.
2 Deviation How much each measurement differs from the mean is an important number and is called the deviation A deviation is associated with each measurement, and if a given deviation is large compared to others in a series of identical measurements, the proverbial red flag is raised. Such a measurement is called an outlier Mathematically, the deviation is calculated as follows: d = |m – e| (1.1) in which d is the deviation, m is the mean, and e represents the individual experimental measure- ment (The bars refer to absolute value, which means the value of d is calculated without regard to sign.)
3 Standard deviation The most common measure of the dispersion of data around the mean is the standard deviation:
In statistics, the term "n" denotes the number of measurements, while "n – 1" indicates the degrees of freedom The standard deviation, represented by "s," plays a crucial role in assessing data precision; a smaller value of s signifies that the measurements are closely clustered around the mean For a theoretical infinite number of measurements, the mean is denoted as "m," and the standard deviation is referred to as the population standard deviation, symbolized by the Greek letter sigma (σ) Practically, an approximation of an infinite number of measurements is achieved with 30 or more data points.
4 Relative standard deviation One final deviation parameter is the relative standard deviation (RSD) It is calculated by dividing the standard deviation by the mean and then multiplying by
Introduction to Analytical Science 11 and relative % standard deviation = RSD ¥ 100 (1.4) and relative parts per thousand standard deviation = RSD ¥ 1000 (1.5)
Relative standard deviation relates the standard deviation to the value of the mean and represents a practical and popular expression of data quality.
The following numerical results were obtained in a given laboratory experiment: 0.09376, 0.09358,
0.09385, and 0.09369 Calculate the relative parts per thousand standard deviation.
We must calculate both the mean and the standard deviation in order to use Equations (1.3) and (1.5).
Next, the deviations: d1=|0.09372 – 0.9376|= 0.00004 d2 =|0.09372 – 0.09358|= 0.00014 d3 =|0.09372 – 0.09385|= 0.00013 d4 =|0.09372 – 0.09369|= 0.00003 Then, the standard deviation:
= 1.14 ¥ 10 - 4 = 1.1 ¥ 10 - 4 Finally, to get the relative parts per thousand standard deviation:
Normal Distribution
In an infinite data set, a plot of frequency of occurrence against measurement value produces a smooth bell-shaped curve, characterized by an equal drop-off on both sides of a peak value, which resembles a bell This peak value represents the population mean (m) and signifies a normal distribution of values for any infinitely repeated measurement Consequently, this curve is known as the normal distribution curve, as illustrated in Figure 1.3.
The normal distribution curve visually represents the precision of a data set, indicating that a higher concentration of data points near the mean, along with a steeper decline away from it, signifies a smaller standard deviation.
In analytical chemistry, understanding deviations is crucial for obtaining precise data Statistically, about 68.3% of the data points lie within one standard deviation from the mean, while approximately 95.5% fall within two standard deviations, highlighting the importance of these metrics in data analysis.
2 standard deviations from the mean, and approximately 99.7% of the area falls within 3 standard deviations from the mean.
Precision, Accuracy, and Calibration
We have made references in the foregoing discussion to the precision of data, or how precise the data are.
We have also made reference to the accuracy of data Precision refers to the repeatability of a measurement.
Precision in measurements is indicated by consistent results that show minimal deviation within the limits of significant figures While precise data reflects a high degree of consistency, it does not guarantee accuracy, which pertains to how closely the measurements align with the true value of the parameter Thus, a precise mean may not necessarily represent the actual value.
To determine the accuracy of a laboratory balance, an analyst can weigh a known object, such as one that weighs exactly 1.0000 g If repeated measurements on the balance consistently fall within the range of 0.9998 to 1.0002 g, the balance is considered both precise and accurate Conversely, if the measurements vary between 0.9983 and a lower value, it indicates a lack of accuracy in the balance.
A balance reading of 0.9987 g indicates precision but not accuracy If repeated measurements range from 0.9956 to 0.9991 g, the data lacks both precision and accuracy Conversely, if the measurements fall between 0.9956 and 1.0042 g, with a mean of 1.0000 g, the balance is deemed accurate but not precise These concepts of accuracy and precision are further illustrated in Figure 1.4.
Calibration is the process of verifying that a measuring device, such as an analytical balance or pH meter, provides accurate values for known samples within established precision limits This involves checking the device against known standards, and in some cases, electronically adjusting it to ensure accuracy For instance, a pH meter is calibrated using solutions with known pH values, while a spectrophotometer determines absorbance values for known concentrations Understanding these calibration methods is essential for our studies.
FIGURE 1.3 The normal distribution curve.
* Standard weights certified by the National Institute of Standards and Technology, NIST, are available.
Statistical Control
A device, procedure, or method is considered to be in statistical control when its regularly derived numerical values consistently fall within 2 standard deviations of the established mean, occurring 95.5% of the time If two or more consecutive values exceed this range, it signals a potential problem, as such occurrences should only happen 4.5% of the time, or approximately once every 20 events Therefore, repeated deviations indicate that the process is out of statistical control and requires further evaluation.
If a single numerical value deviates from the established mean by more than three standard deviations, it signals a potential issue, as such occurrences should only happen 0.3% of the time, or roughly once in every 333 events Therefore, a thorough evaluation is necessary.
Analytical laboratories, particularly those focused on quality assurance, routinely maintain control charts to provide a visual history of devices, procedures, and processes These graphical records, updated daily, plot numerical values on the y-axis against dates on the x-axis, allowing scientists and technicians to easily monitor and assess the performance and stability of their methods at a glance.
The chart features five horizontal lines that indicate key numerical values essential for statistical control Among these, one line represents a value that is three standard deviations above the optimal value, while another line marks a value three standard deviations below it These critical values are anticipated to occur less than 0.3% of the time, highlighting their significance in statistical analysis.
These two numerical values are called the action limits because one point outside these limits is cause for action to be taken.
Two additional horizontal lines are positioned at values that are two standard deviations away from the ideal value, one above and one below, indicating values that are anticipated to occur only 4.5% of the time The fifth line represents the desirable value itself Refer to Figure 1.5 for illustration.
FIGURE 1.4 Illustration of precision and accuracy.
Devices that undergo regular calibration checks, such as analytical balances, can be effectively monitored by testing them with known weights The known weight serves as the target value, while the expected precision range establishes the warning and action thresholds.
A quality control solution, commonly referred to as a control, is utilized to verify a procedure or method by comparing its measured concentration value to a known standard This known value serves as the desirable target on a control chart The results obtained from the procedure are plotted on the chart, while warning and action limits are established based on preliminary analyses conducted enough times to determine the population standard deviation.
Control charts are essential tools for monitoring manufacturing processes, as they help establish desirable values, warning limits, and action limits for products over time By utilizing reliable materials and equipment, scientists and engineers can ensure accurate assessments of product quality throughout the manufacturing process.
Experiment 1: Assuring the Quality of Weight Measurements
To ensure accurate measurements in the laboratory, it is essential to maintain a permanent log and a quality control chart for each analytical balance Users must record their name and the date each time they utilize a specific balance Additionally, a calibration check should be conducted weekly on all analytical balances to uphold precision and reliability in results.
If the calibration of your analytical balance has not been checked in over a week, it is essential to perform the calibration procedure as outlined in Section 3.3 for proper usage and accuracy.
1 Obtain a certified 500-mg standard weight or other weight suggested by your instructor Do not touch the weight, but handle it with tweezers, and never allow any water or other foreign material to touch it.
2 Check the calibration of the analytical balance you have chosen to use by weighing this standard weight on this balance When finished, store the standard weight in the specified protected location.
FIGURE 1.5 An example of a control chart showing a device, procedure, process, or method that is in statistical control because the numerical values are consistently between the warning limits.
Upper Action Limit Upper Warning Limit
3 Along with your name and date in the logbook, also record the measured weight of the standard weight.
4 Plot your measured weight on the control chart If any irregularity is observed, report to your instructor.
Experiment 2: Weight Uniformity of Dosing Units
Reference: General Test , U.S Pharmacopeia and National Formulary, USP 24–NF 19, 2000, p 2000.
1 Randomly collect ten ibuprofen tablets from a bottle of ibuprofen from a pharmacy.
2 Handling the tablets with tweezers, carefully weigh each on an analytical balance (see Section 3.3 and Appendix 1).
3 Calculate the mean, standard deviation, and relative percent standard deviation of this data set.
4 Evaluate the results from step 3 Comment on the uniformity of the tablet weight Also note the milligrams of ibuprofen per tablet found on the label and compare this with your results If the label value is less than the mean you calculated, give some possible reasons for this.
1 Define analytical science, analysis, chemical analysis, analyte, matrix, and assay.
2 When is an analysis an assay and when is it not? Give examples of both.
3 Distinguish between qualitative analysis and quantitative analysis Give examples.
4 Imagine that you are an analytical chemist and someone brings you an oily rag to analyze in order to identify the material on the rag Is this a qualitative or quantitative analysis?
5 Distinguish between wet chemical analysis, instrumental analysis, and analysis using physical properties.
6 Imagine taking a tour of an industrial facility and having a particular laboratory being described to you as the “wet lab.” What do you suppose is the kind of activity going on in such a laboratory?
7 When would you choose a wet chemical analysis procedure over an instrumental analysis proce- dure? When would you choose an instrumental analysis procedure over a wet chemical analysis procedure?
8 What are the five steps in the analytical strategy?
9 What is a sample? What does it mean to obtain a sample?
10 What does it mean to prepare a sample?
11 What is an analytical method, and how does it fit into the total analysis process?
12 What does it mean to carry out the analytical method?
13 What happens after a chemist acquires data from an analytical method?
14 What does it mean to say that a laboratory worker has good analytical technique?
15 Why should a stirring rod that is removed from a beaker containing a solution of the sample being analyzed be rinsed back into that solution with distilled water?
17 What sort of things do the GLP regulations address?
18 Why must good laboratory technique apply to laboratory notebooks as well as to the handling of laboratory equipment and chemicals?
19 What constitutes data and results as recorded in a laboratory notebook?
20 Why should notebook data entries always be made in ink and never erased or otherwise made unintelligible?
21 Given the care with which laboratory equipment (balances, burets, instruments, etc.) is calibrated at the factory, why should the chemical analyst worry about errors?
22 Distinguish between determinate and indeterminate errors.
24 An analyst determines that the analytical balance he used in a given analytical test is wrongly calibrated Is this a determinate or an indeterminate error? Explain.
Introduction
The analysis of a bulk system to identify or quantify an analyte follows a five-step strategy: 1) obtain a sample, 2) prepare the sample for the chosen analytical method, 3) execute the analysis method, 4) process the data, and 5) calculate and report the results This book, along with others, provides extensive detail on step 3 due to the wide variety of methods available, each requiring individual study to understand how they yield the desired results.
No analytical method can yield accurate results if the sample is improperly obtained or prepared The initial steps of sampling and sample preparation are as vital as the analytical method itself, underscoring their significance in the overall analytical strategy Although this book dedicates only one chapter to these topics, their critical importance in ensuring successful analysis should not be overlooked Quality sampling and preparation are essential for achieving reliable analytical outcomes.
Obtaining the Sample
Laboratory analyses are designed to provide results that reflect concentrations within large systems For instance, farmers seek analysis results that indicate fertilizer requirements for an entire 40-acre field, while pharmaceutical manufacturers need data to represent the concentration of active ingredients across multiple cases of their products, which contain numerous bottles and tablets Additionally, governmental environmental agencies rely on single laboratory analyses to assess the concentration of toxic chemicals in extensive areas, such as every cubic inch of soil surrounding hazardous waste sites.
Obtaining a representative sample is crucial in any sampling task, as it must accurately reflect the characteristics and analyte concentration of the entire bulk system This means that the concentration level detected in a sample is assumed to represent the entire system For instance, when analyzing lake water for mercury, if a water sample shows a mercury level of 12 parts per million (ppm), it is inferred that the entire lake has a mercury concentration of 12 ppm, provided the sample is representative.
L1519_Frame_C02.fm Page 17 Monday, November 3, 2003 11:29 AM www.pdfgrip.com
Obtaining samples for analysis involves varying degrees of difficulty and different sampling methods, influenced by factors such as the type of sample, the homogeneity of the source, and accessibility to the system For instance, collecting a blood sample from a hospital patient presents distinct challenges compared to extracting a coal sample from a train car filled with coal.
The quality of a blood sample is influenced by factors such as the collection site, time of day, the patient's diet, and any medications that may impact the analysis Similarly, when sampling coal from a train car, it's crucial to acknowledge the potential heterogeneity of the coal, necessitating a tailored sampling scheme to ensure effective sample preparation.
In laboratory analysis, it is crucial that the sample is representative of the entire system to ensure accurate chemical results Variations in composition, like those found in coal, necessitate collecting small samples from all suspected areas These samples are then combined to create a homogeneous final sample known as a composite sample Alternatively, individual analysis may be more suitable in certain cases, leading to the use of selective samples.
When analyzing soil for nitrogen content, a farmer must consider that different areas of the field may yield varying results, especially if influenced by nearby sources like a cattle feed lot To accurately assess the field's nitrogen needs, the farmer can either take a composite sample that combines soil from all parts of the field or collect selective samples from areas above and below the feed lot This ensures that the chemical analysis accurately reflects the nitrogen levels across the entire field, providing reliable information for fertilizer application decisions.
To assess pesticide residue on tree leaves, growers need to determine if further pesticide application is necessary It is essential for analysts to sample leaves from various parts of the tree, including the top, middle, and bottom, to account for potential differences in pesticide application rates Additionally, leaves from the outer branches and those closer to the trunk should be included, as well as samples from both the shady and sunny sides of the tree Ultimately, all collected leaf samples are combined to create a composite sample for analysis.
Analyzing a blood sample for alcohol content is crucial when a police officer suspects a motorist of intoxication The key challenge lies not in sampling different locations within the body, but in the timing of the blood draw To accurately demonstrate intoxication at the moment the motorist was stopped, the blood must be collected within a specific time frame.
In a homogeneous bulk system, a random sample is selected to assess the concentration of a specific component, such as the active ingredient in pharmaceutical products stored in individual bottles This approach assumes uniformity across the bulk, leading to the selection of a sample without bias towards any particular bottle or box Various terms, including bulk sample, primary sample, secondary sample, subsample, laboratory sample, and test sample, describe the process of dividing a sample from the bulk system for analysis, exemplified by collecting a water sample from a well.
Modern precision agriculture employs GPS technology for effective sampling and accurate determination of fertilizer requirements This approach enhances agricultural productivity and sustainability.
Sampling and sample preparation involve collecting a bulk or primary sample in a large bottle, which is then transferred into a vial to create a secondary sample for laboratory analysis This secondary sample may be poured into a beaker before a specific portion is measured into a flask, where it is diluted to produce the final sample solution for testing.
Sampling issues are distinct to each specific scenario, requiring analysts to consider all potential variations when collecting samples This ensures that the laboratory sample accurately reflects the intended subject matter.
Statistics of Sampling
When discussing sampling, it is essential to consider statistics due to the randomness inherent in sample acquisition Just as random errors in laboratory work are addressed through statistical methods, sampling errors also require statistical analysis Despite efforts to ensure that a randomly acquired sample is representative, variations among samples taken from the same system will always exist to an unpredictable degree.
A common misconception among novices is that a lab analyst simply collects a single sample from a bulk system, conducts one laboratory analysis, and reports the results as definitive While these results may be valid if variances in sampling and lab work are minimal, significant discrepancies can render them unreliable Therefore, as discussed in Chapter 1, the proper approach involves conducting multiple analyses and addressing variances through statistical methods to ensure accurate results.
The treatment of municipal water with chlorine and ammonia produces chloramines, an effective long-lasting disinfectant However, excessive ammonia can lead to increased nitrification by bacteria, raising nitrate and nitrite levels in the water Elevated levels of nitrates and nitrites in drinking water pose significant health risks, especially for infants.
Regular monitoring of nitrate and nitrite levels in water treated with chlorine and ammonia is essential This requires the collection of water samples from both water distribution systems and plant process sites These samples should then be analyzed in a laboratory to ensure water quality and safety.
Allison Trentman and B.J Kronschnabel of the City of Lincoln, Nebraska, Water Treatment Plant Labo- ratory take samples of drinking water from a distri- bution system sampling site.
Sampling introduces an additional statistical challenge, necessitating the collection of multiple samples and the application of statistical methods to analyze the results, similar to conducting repeated laboratory analyses For instance, if a measurement system yields data with a standard deviation of 10 ppm and we aim to determine an average concentration within ±5 ppm at 95% confidence, we must perform the analysis 16 times In scenarios where sampling variance is high but laboratory analysis variance is low, it is essential to analyze 16 individual samples Conversely, if laboratory analysis variance is high while sampling variance is low, measuring a single sample 16 times is required.
If both the sampling variance and the lab analysis variance are high, then we must measure 16 samples each 16 times.
Chemists want to have as low a variance (or standard deviation) as possible for the greatest accuracy.
To achieve a desirable low standard deviation, it is essential to increase the number of measurements, which may involve augmenting either the sample size, the number of laboratory analyses, or both.
If increasing the number of measurements is not desirable (due to an increased workload or expense,etc.), then the analyst must live with a larger error.
Sample Handling
Chain of Custody
Maintaining a documented chain of custody is crucial for ensuring sample integrity from the point of collection to the laboratory analysis Each individual who handles the sample, including the sampling technician, driver, shipping and receiving clerk, subordinate, and laboratory technician, must clearly outline their responsibilities and actions taken during their custody of the sample This documentation process involves recording the sample's journey and maintaining copies of the chain of custody at each stage, which is essential for accountability and traceability in laboratory procedures.
Maintaining Sample Integrity
Sample custodians must preserve the original physical and chemical state of samples to ensure they accurately represent the bulk system regarding analyte identity and concentration Key changes to prevent include the loss of sample matrix or solvent due to evaporation or other factors, as well as the loss of analytes caused by evaporation, chemical reactions, temperature fluctuations, or bacterial activity.
The chain of custody for a water sample collected from a remote site must be thoroughly documented to ensure the integrity of the sample Proper documentation is essential for maintaining quality in analytical laboratories, as highlighted in Kenkel's "A Primer on Quality in the Analytical Laboratory." This process safeguards the reliability of the analysis and supports accurate results.
Sampling and sample preparation are crucial steps that can be affected by various factors, including the presence of interfering analytes from contact with different matrices, contamination from other chemicals, and moisture absorption due to exposure to humid environments.
To prevent evaporation loss, it is essential to seal the sample in its container, ensuring that liquid samples are filled to the brim without any headspace If the sample contains volatile components, it should be stored below room temperature, and caution is necessary when opening the container in the lab During transfer to another container or filter, it is crucial to avoid losing any sample, including residue left on the container walls Additionally, maintaining the cleanliness of the container and any laboratory equipment in contact with the sample is vital for accurate results.
To prevent the loss of analyte due to chemical reactions, temperature fluctuations, or bacterial influences, it is essential to implement specific precautions tailored to the analyte These measures may involve adding preservatives, controlling environmental factors such as temperature and humidity, and protecting samples from sunlight and oxygen Furthermore, all laboratory equipment that interacts with the sample during preparation must be thoroughly cleaned to eliminate any contaminants that could affect the analyte.
For the analysis of metals in environmental water samples, it is recommended to use quartz or Teflon containers, though polypropylene containers are often a more cost-effective alternative Borosilicate glass is acceptable, while soft glass should be avoided due to potential metal leaching When testing for silver, dark-colored containers are necessary, and samples must be preserved with concentrated nitric acid to maintain a pH of less than two, preventing iron precipitation in well water For phosphate analysis, plastic bottles should not be used unless frozen, as phosphates can adhere to plastic surfaces Mercuric chloride, a preservative, should only be utilized when determining total phosphorus All containers intended for phosphate analysis must be acid rinsed, and detergents containing phosphates should be avoided when cleaning sample containers or laboratory glassware.
For accurate analysis of nitrate in environmental water samples, it is essential to analyze them immediately after collection If immediate analysis is not possible, samples can be refrigerated at 4°C for up to 24 hours Alternatively, they can be stored indefinitely at the same temperature if 2 mL of concentrated sulfuric acid is added per liter However, it's important to note that in these stored samples, the differentiation between nitrate and nitrite is not possible.
* Source: Standard Methods for the Examination of Water and Wastewater , 19th edition, APHA, AWWA, 2000.
When handling samples, it is crucial to consider the potential impact of various matrices or chemical systems, such as sample containers, spatulas, scoops, grinders, mixers, and filters Taking proper precautions is essential to prevent any unintended alterations or changes to the sample's composition.
An effective sample custodian possesses the essential analytical laboratory skills detailed in Chapter 1 (refer to Section 1.5) and applies these skills diligently in all laboratory operations A meticulous and responsible laboratory technician plays a crucial role in preserving the integrity of samples.
Sample Preparation: Solid Materials
Particle Size Reduction
Efficient dissolution of solid samples requires the solvent to have intimate contact with small particles, as dissolution occurs only at the particle's outer surface To maximize solvent contact, it is ideal to reduce the particle size to a fine powder, achieved through methods like crushing, milling, grinding, or pulverizing In cases where powdering is not feasible, such as with polymer films or organic tissues, alternative size reduction techniques like cutting, chopping, or blending are employed Common tools used in analytical laboratories for sample preparation include crushers, ball mills, mortars and pestles, scissors, and blenders.
Sample Homogenization and Division
In analytical procedures, the required amount of solid sample may be significantly less than what is available, necessitating the extraction of a representative portion from a larger, homogeneous sample However, particle size reduction methods can compromise the homogeneity of the sample; for instance, crushing large dirt clods from a dried soil sample may produce a powder that is not uniformly mixed To achieve a representative test sample, it is essential to implement a mixing procedure after particle size reduction, followed by a division process to create the necessary portions Additionally, to ensure uniform particle size, samples can be passed through a sieve, as detailed in Chapters 3 and 15.
Solid–Liquid Extraction
An analyte may exist in a solid or liquid sample and needs to be separated from its matrix into a different phase, typically a liquid, through a process known as extraction In solid-liquid extraction, the solid sample is combined with a liquid, allowing the analyte to dissolve while other components remain insoluble This process can be executed in two ways: either by shaking the sample and liquid together, filtering the mixture, and collecting the filtrate containing the analyte, or by employing a Soxhlet extraction method, where fresh liquid is continuously cycled through the solid sample over several hours, usually eliminating the need for filtration Soxhlet extraction will be explored further in Chapter 11.
Other Extractions from Solids
Supercritical fluid extraction is a technique used to extract compounds from solid samples, utilizing a state of matter that is neither liquid nor gas, but rather a unique phase with distinct properties In this state, supercritical fluids exhibit enhanced solvent capabilities compared to their gaseous form and significantly lower viscosities than their liquid counterparts This supercritical state is attained by applying high temperature and extremely high pressure, surpassing the critical temperature and pressure specific to the substance being used.
Supercritical fluids, known for their excellent solvent properties and low viscosities, enable efficient extraction of analytes from solid phase samples In this process, the solid sample is contained in a tube or cartridge, allowing the supercritical fluid to flow through with minimal pressure As the fluid carries the analyte, it passes through a trap solvent where the analyte dissolves, after which the fluid transitions back to the gas phase.
Finally, extractions from solids can be performed by heating followed by solvent trapping Such a procedure is known as thermal extraction.
Fertilizers sold to gardeners and farmers are composed of various granular chemicals, often differing in color due to their distinct chemical compositions To ensure accurate testing of these nonhomogeneous samples, analytical laboratory technicians at the Nebraska State Agriculture Laboratory grind the samples in a grinding mill, which operates similarly to a kitchen blender This process pulverizes the fertilizers, creating a homogeneous mixture suitable for analysis.
Tai Van Ha from the Nebraska State Agriculture Laboratory examines a fertilizer sample that displays a lack of homogeneity, featuring a mix of both light and dark-colored granules within the bag.
Total Dissolution
When extraction is impractical, total dissolution of a sample becomes necessary, requiring the selection of an appropriate solvent capable of fully dissolving the sample For solid samples, this typically entails using water or acid-water mixtures, often including concentrated acid solutions Understanding the role of water and common laboratory acids is essential in this process.
Water is a highly effective solvent due to its polar nature, making it ideal for dissolving polar or ionic substances This property is particularly useful when analyzing samples composed of ionic salts or polar compounds, such as determining the sodium iodide content in commercial iodized table salt For further reference, a comprehensive list of solubility rules for ionic compounds in water is available in Table 2.1.
Hydrochloric acid (HCl) is a strong acid commonly used for sample dissolution when water is ineffective Concentrated HCl, a saturated solution of hydrogen chloride gas, contains approximately 38.0% HCl (about 12 M) and emits a pungent odor This acid is particularly effective for dissolving metals, metal oxides, and carbonates that water cannot dissolve, including iron, zinc, and the scales found in boilers and humidifiers Due to its toxicity, hydrochloric acid must be handled with care and is stored in a blue color-coded container.
Sulfuric acid An acid that is considered a stronger acid than HCl in many respects is sulfuric acid,
Sulfuric acid (H2SO4) is a clear, colorless, and dense liquid, composed of approximately 96% H2SO4 and 4% water When it comes into contact with materials like clothing or paper, it reacts almost instantly, causing paper to turn black and disintegrate while weakening clothing fibers and creating holes Due to its violent reaction with water, which generates significant heat, care must be taken when preparing water solutions of sulfuric acid, often requiring cooling methods Its primary application in dissolution is with organic materials, such as vegetable plants, while its effectiveness with metals is limited, as many metals produce insoluble sulfates.
The preferred solvent for Kjeldahl analysis of grains and grain processing products, this versatile solution also effectively dissolves aluminum and titanium oxides found on aircraft components It is important to note that it is stored in a yellow color-coded container for easy identification.
TABLE 2.1 Solubility Rules for Ionic Compounds in Water
Acetates Yes Silver acetate is sparingly soluble
Chlorides and bromides of silver (Ag), lead (Pb), and mercury (Hg) are generally insoluble, although lead chlorides and bromides can dissolve in hot water In terms of sulfates, barium (Ba) and lead sulfates are insoluble, while those of silver, mercury, and calcium (Ca) exhibit slight solubility Conversely, carbonates of sodium (Na), potassium (K), and ammonium (NH4) are soluble.
Phosphates No Phosphates of Na, K, and NH 4 are soluble
Chromates No Chromates of Na, K, NH 4 , and Mg are soluble
Hydroxides of sodium, potassium, and ammonium are not soluble, while those of barium, calcium, and strontium have slight solubility Additionally, sulfides of sodium, potassium, ammonium, calcium, magnesium, and barium are also insoluble.
Sodium salts Yes Some rare exceptions
Potassium salts Yes Some rare exceptions
Ammonium salts Yes Some rare exceptions
Silver salts No Silver nitrate and perchlorate are soluble; silver acetate and sulfate are sparingly soluble
Nitric acid (HNO3) is a highly corrosive and dangerous oxidizing acid, known for its unique reactions with metals that produce nitrogen oxides and various toxic gases Concentrated nitric acid, which contains 70% HNO3 (16 M), is utilized in applications requiring a strong acid with oxidizing capabilities, such as processing metals like silver and copper, as well as in environmental testing of wastewater samples Due to its hazardous nature, nitric acid can cause skin discoloration upon contact and is stored in red color-coded containers for safety.
Radioactive plutonium isotopes release alpha particles, and the quantity of radioactive plutonium in a sample can be quantified using alpha spectroscopy, a method that counts alpha radiation This technique is employed at the Los Alamos National Laboratory (LANL) in New Mexico to monitor employee exposure levels.
Sample preparation for plutonium analysis involves several intricate steps Urine or fecal samples are treated with calcium phosphate to precipitate plutonium, followed by centrifugation to separate solids These solids are then dissolved in 8 M nitric acid and heated to convert plutonium to its +4 oxidation state The nitric acid solution is passed through an anion exchange column, where plutonium is eluted using a hydrochloric-hydroiodic acid solution After evaporating this solution to dryness, the sample is redissolved in sodium sulfate and electroplated onto a stainless steel planchette Alpha particles emitted from the electroplated material are measured using an alpha spectroscopy system to calculate the ingested radioactive plutonium Annually, around 2000 samples are prepared for this analysis in a clean room environment.
Stephanie Boone, a technician in the Chemistry Division Bioassay Program at Los Alamos National Laboratory, meticulously prepares samples for electroplating, essential for alpha spectroscopy analysis Adhering to clean room protocols, she wears a hair net and a specialized lab coat to maintain a contamination-free environment.
Hydrofluoric acid (HF) is a highly dangerous acid with specific applications, particularly in dissolving silica-based materials like sand, rocks, and glass, as well as stainless steel alloys Its effects on skin can be insidious, initially appearing mild but potentially leading to severe damage if contact is prolonged, especially if the acid is trapped against the skin or under fingernails Treatment for HF exposure is challenging and painful Due to its ability to dissolve glass, concentrated HF, which is approximately 50% HF (26 M), must be stored in plastic containers, a precaution that also applies to low pH fluoride salt solutions.
Perchloric acid Another important acid for sample preparation and dissolution is perchloric acid,
HClO4, a powerful oxidizing acid, surpasses HNO3 in strength when hot and concentrated It is effective for dissolving metals, as metal perchlorates are highly soluble, but its primary utility lies in treating challenging organic materials like leathers and rubbers, often in conjunction with nitric acid Additionally, HClO4 can be applied to stainless steels and stable alloys Commercially available HClO4 is typically 72% concentration (12 M) and poses significant dangers, especially when heated and in contact with organic substances Therefore, it should always be handled in a specialized fume hood to capture its vapors, and precautions must be taken to avoid contact with alcohols and other oxidizable materials to prevent explosive reactions.
Aqua regia is a potent acid mixture created by combining one part concentrated nitric acid (HNO3) with three parts concentrated hydrochloric acid (HCl) Renowned for its exceptional dissolving capabilities, aqua regia can dissolve noble metals such as gold and platinum, as well as highly stable alloys.
Table 2.2 summarizes these acids and their properties Occasionally, organic liquids are also used for total sample dissolution Common laboratory organic solvents are described in Section 2.6.
TABLE 2.2 Various Laboratory Acids and Their Properties
Name Formula Description Example Uses
Water H 2 O Clear, colorless liquid with low vapor pressure, highly polar
Dissolving polar and ionic compounds
HCl Commercially available concentrated solution is 38% (12 M ) HCl; evolves pungent fumes and must be handled in fume hood
Dissolving some metals and metal ores
Sulfuric acid H 2 SO 4 Commercially available concentrated solution is 96% (18 M ) H 2 SO 4 ; a dense, syrupy liquid; reacts on contact with skin and clothing; evolves much heat when mixed with water
Organic samples, such as for Kjeldahl analysis (see Chapter 5); also oxides of Al and Ti
Nitric acid HNO 3 Commercially available concentrated solution is 70% (16 M ) HNO 3 ; reacts with clothing and skin (turns skin yellow); evolves thick brown and white fumes when in contact with most metals
Dissolving noble metals (e.g., copper and silver) and also some organic samples
HF Commercially available concentrated acid is
50% (26 M ) HF; must be stored in plastic containers, since it attacks glass; very damaging to skin
Dissolving silica-based materials and stainless steel
Perchloric acid HClO 4 Commercially available concentrated solution is 72% (12 M ) HClO 4
Dissolving difficult organic samples and stable metal alloys
Aqua regia — A mixture of concentrated HNO 3 and HCl in the ratio of 1:3 HNO 3 :HCl
Dissolving highly unreactive metals, such as gold
Fusion
For challenging samples, the fusion method is utilized, which involves dissolving the sample in a molten inorganic salt known as a flux This process results in a solid mass upon cooling, making it soluble in a liquid reagent The effectiveness of the flux is attributed to the high temperatures, typically ranging from 300 to 1000°C, necessary to melt most inorganic salts.
Fusion methods face additional challenges, primarily the requirement for a substantial amount of flux to achieve successful results This large quantity must not interfere with the measurement of the analyte Furthermore, while flux can effectively dissolve difficult samples, it may also partially dissolve the container, leading to contamination issues Although platinum crucibles are commonly employed, alternatives such as nickel, gold, and porcelain have proven effective for certain applications.
Common fluxes include sodium carbonate (Na2CO3), lithium tetraborate (Li2B4O7), and lithium metaborate (LiBO2), which can be utilized alone or in combination with oxidizing agents like nitrates, chlorates, and peroxides These fluxes are essential in various applications, particularly in the processing of silicates, silica-based samples, and metal oxides.
For dissolving particularly difficult metal oxides, the acidic flux potassium pyrosulfate (K2S2O7) may be used.