In the Laboratory
Antacids Revisited with Modern Chemical Instruments: GCMS, AAS, and CCT
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Stanley L. Burden and Christopher J. Petzold Chemistry Department, Taylor University, Upland, IN 46989;
[email protected] Introduction and Overview A number of reports describing the chemistry and analysis of antacids appear in the literature (1–4 ), and commercial antacids have been utilized in laboratory experiments designed for general chemistry or analytical chemistry for many years. The simplest of these experiments require students to determine the acid-neutralizing capacity of the antacids by manual titration (5, 6 ); more advanced experiments probe their physiological behavior (7–9). A somewhat more sophisticated analytical experiment utilizing antacids results if students are given a commercial antacid, asked to determine its brand name, and required to support their conclusions with several types of analyses and proper statistical treatment of data. In the experiment described in this paper, students receive a ground sample of a commercial antacid and a list of names of 6–8 antacids, among which is the name of their sample. After suitable discussion in class of principles and major steps in the process, students complete the design of a series of experiments employing computer-controlled titrations (CCT), atomic absorption spectrometry (AAS), and gas chromatography–mass spectrometry (GCMS). As part of this procedure, students also design and carry out a series of manual titrations to statistically compare the acid-neutralizing capacity (ANC) of their unknown to that of the commercial antacid that they believe matches their unknown. This provides the final bit of confirming evidence for their identification of their unknown. Students use a visual indicator, which they choose on the basis of their titration curves, in these manual titrations. They then report their results in standard manuscript format. Such an experiment typically takes three to four 3-hour laboratory periods in analytical chemistry, depending on the amount of information and help students receive. The project
Figure 1. Titration curves for sample salts dissolved in deionized water (DIW)s at pH = 2. A: 0.3 g Na2CO 3 in 50 mL DIW; B: 0.3 g Mg(OH)2 in 40 mL DIW; C: 0.9 g Al2(SO4)3?18H 2O in 40 mL DIW; D: 0.1 g CaCO3 in 50 mL DIW.
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gives students experience using several instrumental methods, in designing experiments that provide valid statistical comparisons, and in integrating information from several techniques to confirm their answers. Students usually do this experiment after they have covered statistical concepts in class. They begin it along with the study of acid–base titrations. Depending on the complexity of experience desired, students can be given reference titration curves for direct comparison or they can be asked to interpret the CCT curves they obtain on their unknown and then run knowns until they find a match. Since there are multiple inflections in several of the CCT curves for the antacids employed, the interpretation of these provides a good review of the chemistry involved. The more accurate the student’s
Figure 2. Titration curves for commercial antacids. A: Digel (280 mg calcium carbonate, 128 mg magnesium carbonate, 20 mg Simethicone), 0.1 g in 50 mL DIW. B: Rolaids 1995 (300 mg dihydroxyaluminum sodium carbonate), 0.1 g in 100 mL DIW. C: Rolaids 1996 and later (412 mg calcium carbonate, 80 mg magnesium hydroxide), 0.5 g in 50 mL DIW. D: Maalox (200 mg magnesium hydroxide, 200 mg dried aluminum hydroxide gel, 25mg Simethicone), 0.7 g in 100 mL DIW. E: Tums (500 mg calcium carbonate), 0.5 g in 30 mL DIW. F: Rite Aid Magnesia (311 mg magnesium hydroxide), 0.1 g in 30 mL DIW. G: Alkamints (850 mg calcium carbonate), 0.5 g in 50 mL DIW. H: Gaviscon Extra Strength (160 mg aluminum hydroxide, 105 mg magnesium carbonate), 0.5 g in 50 mL DIW.
Journal of Chemical Education • Vol. 76 No. 11 November 1999 • JChemEd.chem.wisc.edu
In the Laboratory
Figure 3. Total ion chromatograms from the HPGCD for commercial antacids, all samples at pH = 2. A: Digel, 0.1 g in 50 mL DIW. B: Rolaids, 0.1 g in 50 mL DIW. C: Rolaids 96, 0.5 g in 50 mL DIW. D: Maalox, 0.7 g in 100 mL DIW. E: Tums, 0.5 g in 20 mL DIW. F: Rite Aid Magnesia, 0.1 g in 35 mL DIW. G: Alkamints (Red), 0.5 g in 50 mL DIW. H: Gaviscon Extra Strength, 0.5 g in 50 mL DIW.
Table 1. Atomic Absorption Results Antacid
Atom Mg a
Al b
Ca c
Active
Inactive
Gaviscon
D
D
< DL
Al, Mg
—
Rolaids
D
D
< DL
Al
Mg
Maalox
D
D
I
Al, Mg
—
Digel (white)
D
I
D
Ca, Mg
—
Rolaids 1996
D
D
D
Ca, Mg
—
Tums
I
< DL
D
Ca
—
Magnesia
D
< DL
I
Mg
—
Maalox HRF
D
D
I
Al, Mg
—
Note: DL = detection limit, the maximum signal produced by deionized water without re-zeroing the instrument after running one or more samples; D = detected, signal clearly >DL; I = inconclusive result (signal DL, but substance was not listed as either an active or an inactive ingredient in the known reference antacid). aConcentration of standards, 0 and 1.48 ppm; DL = 0.1 ppm bConcentration of standards, 0 and 57 ppm; DL = 8 ppm. cConcentration of standards, 0 and 8.2 ppm; DL = 1 ppm.
initial interpretation is, the fewer trials on knowns he or she needs to make. To help students interpret their titration curves, we furnish them with titration curves of several selected salts dissolved in acid and titrated with base to which they can compare their unknown antacid titration curve and infer possible components. For example, in class we hand out and discuss titration curves of Na2CO3, Al2(SO4)3, Mg(OH)2, and CaCO3 (Fig. 1). The curve for Na2CO3 in Figure 1A clearly shows the inflections due to the titration of bicarbonate and carbonate ions. Figure 1B shows the plateau around pH = 10 due to the presence of magnesium. The aluminum salt in Figure 1C shows the characteristic plateau around pH = 4, which is due to the presence of aluminum species. The CaCO3 curve in Figure 1D displays the effect of a sufficiently high concentration of calcium to cause calcium carbonate to begin forming. This occurs when the concentration of carbonate being formed in the titration becomes sufficiently high that the solubility product for calcium carbonate is exceeded. The effect on the curve is to begin leveling the plateau around pH = 9 and make the inflection due to excess hydroxide ion more distinct than that in the titration curve for sodium carbonate. The relatively large concentration and small volume of titrant used are a function of the particular CCT system we employ. Figure 2 shows titration curves for eight common antacids we typically use. Note that Rolaids purchased prior to 1996 contained aluminum, but in 1996 the formulation was changed to contain calcium and magnesium. Similarly, reference total ion chromatograms (TICs) from the GCMS can be furnished, or not, depending on the time allotted and the sophistication of experiment desired. Figure 3 shows TICs for eight of the antacids we use. We normally allow students to see the TICs of the reference antacids so they can compare the TICs they obtain on their unknowns with them directly. The mass spectrum associated with each of these is also available to the students. By comparing mass spectra, students can confirm that peaks occurring in their TICs at slightly different retention times from peaks in the reference TICs are or are not produced by similar species. Additionally, the instructor or TA normally has the AA and GCMS set up and either runs each student’s sample as the student watches or assists the students closely as they run the samples, so extensive training on the instruments is not required. Since only qualitative results from the AA are needed, careful quantitative calibration is not necessary. Table 1 shows typical results of the AA tests. Interferences make some of the trials inconclusive, but overall the results help students decide among two or three possible choices and force them to consider how to handle inconclusive results. Our students do this experiment in the first term of analytical chemistry, before taking instrumental analysis. This sequence permits them to use the AA and GCMS as tools but actually learn to operate the instrument in detail in the second (instrumental) term of the course. Student Results Figure 4 shows typical student results. Figure 4A shows the titration curve for the unknown antacid. Reflecting on the titration curves for the salts shown in Figure 1, the student observed that the inflections most nearly correspond to those expected from the formation of bicarbonate and carbonate ions. No inflection corresponding to aluminum is present and
JChemEd.chem.wisc.edu • Vol. 76 No. 11 November 1999 • Journal of Chemical Education
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In the Laboratory
the presence of magnesium is possible but not clear. Table 2 shows the results of the AA tests. The presence of calcium and magnesium are clearly indicated; the presence of aluminum is questionable but it is probably absent. Figure 4B shows the TIC from the GCMS for the methylene chloride extract of the unknown antacid. Comparison with the reference TICs, such as those shown in Figure 3, shows the closest match to be with Figure 3C. The mass spectra of peaks at 10.03, 14.86, and 15.80 in the antacid TIC show that these peaks arise from the same species as those that produced peaks 10.06, 14.89, and 15.84 in the reference TIC. A sample of one such mass spectrum, that for the 14.86 peak, is shown in Fig. 4C. Therefore, even though there are some minor differences between the unknown antacid and reference TICs, the correspondence of the mass spectra of the peaks suggests that the antacid is likely the same as the one from which Figure 3C was derived, Rolaids 1996. Since Rolaids 1996 has CaCO3 and Mg(OH)2 as active ingredients, this is consistent with the CCT and AA results. The student then ran a computercontrolled titration on a known sample of Rolaids 1996 and obtained a CCT curve very similar to Figure 4A. To provide the fourth type of evidence in support of her conclusion, the student then designed a two-group experiment to determine the mean ANC value of both her unknown and Rolaids 1996 using manual titrations and a visual indicator of her choice. She then compared the means statistically. By inspecting the titration curves for her unknown and Rolaids 1996 she determined that a suitable visual indicator was bromophenol blue with a transition pH of 3.5. Table 3 displays the results of triplicate manual titrations on both the unknown and Rolaids 1996. Hypothesizing that the means are the same and comparing the means using the appropriate t test shows clearly that the hypothesis cannot be rejected until the 80% confidence level. This implies that the similarity of ANC values is consistent with the two samples being the same compound. In turn, this conclusion is consistent with the data from the CCT, the AA, and the GCMS data. This confirms the identification of the unknown as Rolaids 1996.
Figure 4. Typical student results. A: CCT curve of unknown. B: TIC of unknown. C: Mass spectrum of peak at 14.86 minutes.
Discussion This experiment provides experience for the students in using several analytical techniques to confirm an analysis, encourages them to integrate and apply principles from several major topics covered in analytical chemistry, and forces them to design portions of their own experimental protocol to carry out the analysis. Additionally, it provides an interesting and useful application for computer-controlled titrators, which are becoming more prevalent in undergraduate laboratories. While the titrators our students used were locally designed and constructed, other models have been reported (10–13) or are available commercially.1 Frequently, such tiTable 2. Example of Student Unknown Atomic Absorption Results Sample Standard
Magnesium (± 0.1 ppm)
Aluminum (± 7 ppm)
3
1.5
54
{0.1
Blank Unknown
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Calcium (± 0.5 ppm)
869
0.04
2
6.2
7
Table 3. Example of Student Two-Group Acid Neutralizing Capacity Comparison Trial
Mass of Antacid/g
Titrant Added/mL HCl 0.0609 N
NaOH 0.04151 N
ANC/ meq g {1
Unknown 1
0.2339
33.90
10.42
6.824
2
0.2341
33.64
10.80
6.678
3
0.2340
33.20
10.14
6.693
Av SD %RSD
6.73 0.08 1.2
Rolaids 1996 1
0.2338
34.30
11.48
6.727
2
0.2338
34.20
10.90
6.813
3
0.2343
33.50
10.10
6.770
Av SD %RSD
Journal of Chemical Education • Vol. 76 No. 11 November 1999 • JChemEd.chem.wisc.edu
6.77 0.04 0.63
In the Laboratory
trators are used primarily to demonstrate shapes of titration curves of common strong and weak acids. This experiment provides an additional use for these titrators as an analytical tool, encourages students to interpret the chemistry involved at the various inflections, and requires them to apply these interpretations to solving an analytical problem. The sophistication level and time required to carry out this experiment could easily be increased or decreased depending on the information and equipment made available to the students. We have used some form of this experiment for the past 12 years in our analytical chemistry course. Students virtually always get the correct answer. Grades are based on data quality, reasoning, and style used to present the results in the final report. We added the GCMS portions for the first time last year. Since the data from that portion of the experiment are quite definitive, students had more confidence in their answers and overall reasoning. In all offerings, students rate their experience doing this experiment very positively and recommend that it be continued. Acknowledgments We are grateful to the National Science Foundation for ILI grants, which partially supported the purchase of the atomic absorption spectrometer (Grant #DUE-9350770) and the GCMS (Grant #DUE-9650064) that were used in this experiment.
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The following supplementary materials for this article are available on JCE Online at http://jchemed.chem.wisc.edu/Journal/issues/1999/ Nov/abs1544.html: a list of equipment and chemicals; instructor’s notes for student handouts and general hints; and a handout for students describing the application experiment and its write-up. 1. LabWorks II; SCI Technologies: Bozeman, MN.
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