1.1-post-lab-discussion.docx

PH-PHR 124 LABORATORY: PHARMACEUTICAL ANALYSIS I POST LABORATORY DISCUSSION EXPERIMENT NO. 2 POTENTIOMETRIC ASSAY OF SODIUM PHOSPHATES ENEMA, USP Members: EXPLORATORY TITRATION Hemedes, Ma. Isabel Jan Mohammad, Sultan Javier, Arjielene Legaspi, Therese Chrisyelle Matibag, Gwyneth Miranda, Andrea Ray Montes, Sat Gian Carlos Manuel Noriega, Therese Ma. Dulce Nuestro, Leila Jenine BLANK DETERMINATION Olarve, Jahzeel Kezia Ortiz, Jan Reynee G. Santos, Maria Angelica C. Subion, Joe Mari L. Sucgang, Caitlin Marie T. Tallod, Emerson John Vinoya, Paulyne Grace Yulo, Ralph Liam Yulores, Elaiza Mae M. BSP 1-1 Date Performed: March 12, 2019 Date Submitted: March 29, 2019

I. Principles Involved The type of titration involved in this experiment is residual potentiometric titration. 0.5 N hydrochloric is to be titrated to the sodium phosphate enema solution and then the excess unreacted sodium hydroxide will be back titrated with the excess standard acid. Blank determination is performed by titrating the same amount of the base, added to the sample, to the standard acid. The difference between the volume of the titrant used in the blank determination and the sample is the volume of the titrant equivalent to the sample (Remington, 1987). In this assay, neutralization reaction takes place between sodium hydroxide and hydrochloric acid. The indicator to be used is the pH meter. The endpoint is to be detected through observation of inflection point where drastic change in pH will be recorded. The endpoint of this titration is to be computed using the inflection point values recorded. II. Official Requirement/s Sodium phosphate rectal solution is a solution of dibasic sodium phosphate and monobasic sodium phosphate, or dibasic sodium phosphate and phosphoric acid, in purified water. It contains, in each 100 mL, not less than 5.4 g and not more than 6. g of dibasic sodium phosphate (Na2HPO4 * 7H2O), and not less than 14.4 g and not more than 17.6 g of monobasic sodium phosphate (NaH2PO4 * H2O). III. Assay Procedure (USP 37/NF 32) Pipet 5.0 mL of rectal solution into a 250-mL beaker, and add 15.0 mL of rectal solution of 0.5 N sodium hydroxide VS and 95 mL of water. Titrate the excess base potentiometrically with 0.5 N hydrochloric acid VS to the first inflection point, at a pH of about 9.2. Record the volume, A, in mL, of 0.5 N hydrochloric acid consumed. Continue titration to the second inflection point, at a pH of about 4.4, and record the total volume, B, in mL, of 0.5 N hydrochloric acid required in the titration. For a blank determination, transfer 15.0 mL of 0.5 N sodium hydroxide into a 250-mL beaker, add 100 mL of water, and immediately titrate potentiometrically with 0.5 N hydrochloric acid VS. Record the volume, C, in mL, of 0.5 N hydrochloric acid consumed. Each mL of the volume (C - A) of 0.5 N of 0.5 N hydrochloric acid is equivalent to 69.0 mg of monobasic sodium phosphate (NaH2PO4 * H2O). Each mL of the volume (B - C) of 0.5 N hydrochloric acid is equivalent to 134.0 mg of dibasic sodium phosphate (Na2HPO4 * 7H2O). IV. Reasons for Important Steps Determination of endpoint through potentiometric titration is done because it is more accurate than colorimetric titration (Andres et al., 2015). In addition to that, potentiometric titration is suitable for titration of turbid solutions (Abdellatef, 2010) and

detection of unsuspected species. Moreover, potentiometric titration is warranted to identify the analyte's concentration (Skoog, 2014). Magnetic stirrer is used, rather than manual stirring, because it stirs the solution constantly and uniformly (Andres et al., 2015). Also, it ensures that no disturbance will occur during the titration. Disturbances "will make it difficult for the electrode to equilibrate with the solution and obtain its pH." Glass electrode is used in pH determination because it operates robustly on wide range of pH levels and responds faster. In addition to that, it is less sensitive to interfering ions (Bolan & Kandaswamy, 2004). The electrode should be thoroughly washed before use to prevent contamination of the analyte. Blotting with the use of a tissue paper is done to prevent generation of static charge. If wiping or rubbing is done, the electric charge generated may affect the response time of the electrode during determination of analyte's pH. Moreover, the electrode must not touch the sides of the beaker for accurate results (Andres et al., 2015). Sodium phosphate rectal solution is used due to its amphoteric character: a base when reacted to HCl, and an acid when reacted with water. Water is also added to dissolve and ionize the sodium phosphate to complete the reaction (Andres et al., 2015). Na3PO4 + H2O Na2HPO4 + H2O NaH2PO4 + H2O

Na2HPO4 + NaOH NaH2PO4 + NaOH H3PO4 + NaOH

Sodium hydroxide is added to make the sodium phosphate enema solution basic. Also, "strong base, such as sodium hydroxide, is added to the acid solution, the available hydroxide ions combine with some of the available H+ ions to form water." Large increments of NaOH will be added at the start to hasten titration and because the increase in the pH level is still "small or essentially nonexistent" (Skoog, 2014). Small increments of NaOH must be added to the rectal solution after the first endpoint has been reached to prevent sudden increase of pH. Moreover, dropwise increments should be added until the first equivalence point has apparently passed to determine exact endpoint (Andres et al., 2015). Hydrochloric acid, on the other hand, is a strong monoprotic acid which ionizes completely in water. Due to this condition, "a large reserve of H+(actually H3O+) ions available in solution toinstantly react with any added base." Adding few quantities of the base will result to little change in the pH. In addition to that, NaOH increments added throughout the procedure are immediately neutralized, retaining the pH level (Haminh, 2010). In this experiment, large amount of HCl will be used because the back titration will consume a large amount of the reagent.

Back titration will be done because direct titration of sodium hydroxide is difficult due its cloudy suspension and portions of the solution may cling to the sides of the flask, preventing complete titration and altering the measurement of the endpoint. The pH of 9 is to be observed in the first reaction Na 3PO4 + HCl Na2HPO4 + NaCl to indicate conversion to sodium hydrogen phosphate . A pH of 4 is to be observed in the second reaction, to indicate completion of the second reaction (Hamilton, 1964). V. Proper Disposal and/or Precautions Sodium phosphate is known to cause eye irritation and/or inflammation. For storage, it must be kept in a well-ventilated, dry and cool area. To dispose this reagent it must be diluted with sufficient amount of water prior to disposal. Sodium hydroxide, on the other hand, may also cause eye and skin irritation. For storage, it must also be kept in a well-ventilated, dry and cool area away from strong acids and metals. To dispose this reagent, it must be first treated with an acidic reagent, then diluted with sufficient amount of water prior to disposal to sink. Lastly, while working with hydrochloric acid, its vapors must never be inhaled. Exposed areas must be washed with soap after using the chemical. To dispose the chemical, it must be first neutralized with a base prior to disposing it down the drain.

VI. Chemical Equations Involved First endpoint: Na3PO4 + HCl Na2HPO4 + NaCl Second endpoint: Na2HPO4 + HCl NaH2PO4 + NaCl Na3HPO4 + 2HCl NaH2PO4 + NaCl Titration: NaOH + HCl

NaCl + H2O

The factor in this equation is 2, because there are 2 moles of replaceable H + ions involved in the reaction.

VII. Data Analysis A. Actual Titration

V 0 1 2

pH 11.96

ΔpH -0.47

11.49

Exploratory Titration ΔV 1st Derivative 2

2nd Derivative

-0.235 -0.49

3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22

-2.43

2

-1.215

9.06

0.32 -1.15

2

-0.575

7.91

0.175 -0.45

2

-0.225

7.46

0.0275 -0.34

2

-0.17

7.12

0.01 -0.3

2

-0.15

6.82

-0.005 -0.32

2

-0.16

6.5

-0.0525 -0.53

2

-0.265

5.97

-0.49 -2.49

2

-1.245

3.48

0.4625 -0.64

2

-0.32

2.84

0.1 -0.24

2

-0.12

2.6 Table 1. Potentiometric data for exploratory titration

pH against volume 14 12 10

pH

4, 9.06 8 6

16, 5.97

4

Series1

18, 3.48

2 0 0

5

10

15

20

25

Volume of 0.5 N HCl VS (mL)

Figure 1. Graph of pH against volume of titrant for exploratory titration The equivalence points are barely visible in the curve. The volume at the 1st equivalence point is approximately 4.00 mL, and 18.00 mL for the second equivalence point.

first derivative vs Δvolume 0 0

5

10

15

20

25 21, -0.12

-0.2

first derivative

-0.4 -0.6 Series1

-0.8 -1 -1.2 -1.4

3, -1.215

17, -1.245

ΔVolume of 0.5 N HCl VS (mL)

Figure 2. Graph of ΔpH/ΔV against volume of titrant for exploratory titration

The equivalence points are visible, showing greater accuracy. The first maximum point indicates that the volume at the first equivalence point is 3.00 mL. While the second maximum point indicates that the volume at the second equivalence point is 17.00 mL.

second derivative against Δvolume 0.6 4, 0.32

second derivative

0.4

0.4625

0.2 0 0

5

10-0.005

-0.2

14

15

20, 0.1 20

25

Series1

-0.4 -0.6

-0.49

16, -0.49

ΔVolume of 0.5 N HCl VS (mL)

Figure 3. Graph of Δ (ΔpH/ΔmL)/ΔmL volume of titrant for exploratory titration At the first equivalence point, the curve passed through the x-axis at volume 4.00 mL, indicating that it is the volume at 1st equivalence point. At the second equivalence point, the curve passed through the x-axis at volume 16.00 mL, indicating that it is the volume at 2nd equivalence point. This volume will serve as the equivalence volume which reacted with phosphoric acid in a 2:1 ratio: 2 mol OH- ≡ 1 mol H3PO4 (Cruz, 2014). Final Titration 2nd Derivative V

pH

ΔV

ΔpH

1st Derivative

26.5 28.5

12.1 11.6

2

-0.5

-0.25

29

11.27

0.5

-0.33

-0.66

-0.82

29.5

10.91

0.5

-0.36

-0.72

-0.12

30

9.87

0.5

-1.04

-2.08

-2.72

30.5

8.79

0.5

-1.08

-2.16

-0.16

31

8.49

0.5

-0.3

-0.6

3.12

31.5

8.19

0.5

-0.3

-0.6

-7.1E-15

32

7.99

0.5

-0.2

-0.4

0.4

32.5

7.89

0.5

-0.1

-0.2

0.4

33

7.75

0.5

-0.14

-0.28

-0.16

33.5

7.63

0.5

-0.12

-0.24

0.08

34

7.56

0.5

-0.07

-0.14

0.2

34.5

7.46

0.5

-0.1

-0.2

-0.12

38.5

6.82

4

-0.64

-0.16

0.01

42.5

6

4

-0.82

-0.205

-0.01125

43

5.78

0.5

-0.22

-0.44

-0.47

43.5

5.41

0.5

-0.37

-0.74

-0.6

44

4.08

0.5

-1.33

-2.66

-3.84

44.5

3.56

0.5

-0.52

-1.04

3.24

45

3.24

0.5

-0.32

-0.64

0.8

45.5

3.1

0.5

-0.14

-0.28

0.72

46

2.98

0.5

-0.12

-0.24

0.08

46.5

2.87

0.5

-0.11

-0.22

0.04

Table 2. Potentiometric data for final titration

14

12

10

8

6

4

pH vs vol

First derivative 2

2nd derivative

0 0

5

10

15

20

25

-2

-4

-6

ΔVolume of 0.5 N HCl VS (mL)

Figure 4. Overall graphical presentation for the pH curve (blue), first derivative curve (red), and second derivative curve (green) for the final titration of the actual titration

In the pH curve, the equivalence points are barely visible in the curve. The volume at the 1st equivalence point is approximately 4.00 mL, and 17.50 mL for the second equivalence point. According to Cruz (2014), "adding large amounts of sodium hydroxide solution, titrating with smaller, uniform increments tends to equilibrate the reacting vessel, stabilizing the mixture faster than using bulk amounts." In the first derivative curve, the equivalence points are visible, showing greater accuracy. The first minimum point indicates that the volume at the first equivalence point is 4.00 mL. While the second maximum point indicates that the volume at the second equivalence point is 17.50 mL. According to Cruz (2014), "the first derivative of a titration curve, therefore, shows a separate peak for each end point. The first derivative is approximated as ΔpH/ΔV, where ΔpH is the change in pH between successive additions of titrant." Moreover, the first derivative "gives the titration curve’s slope at each point along the x-axis" and will indicate the equivalence point when "the slope reaches its maximum value at inflection point." In the second derivative curve, at the first equivalence point, the curve passed through the x-axis at volume 4.00 mL, indicating that it is the volume at 1st equivalence point. At the second equivalence point, the curve passed through the x-axis at volume 17.50 mL, indicating that it is the volume at 2nd equivalence point. This volume will serve as the equivalence volume which reacted with phosphoric acid in a 2:1 ratio: 2 mol OH- ≡ 1 mol H3PO4 (Cruz, 2014).This is helpful because, in the second derivative, "equivalence point intersects the volume axis. EXPLORATORY TITRATION pH Curve 1st Equivalence Point

4.00 mL

2nd Equivalence Point

18.00 mL

FIRST DERIVATIVE 1st Equivalence Point

3.00 mL

2nd Equivalence Point

17.00 mL

SECOND DERIVATIVE 1st Equivalence Point

4.00 mL

2nd Equivalence Point

16.00 mL

FINAL TITRATION pH curve 1st Equivalence Point

4.00 mL

2nd Equivalence Point

17.50 mL

FIRST DERIVATIVE

1st Equivalence Point

40.00 mL

2nd Equivalence Point

17.50 mL

SECOND DERIVATIVE 1st Equivalence Point

4.00 mL

2nd Equivalence Point

17.50 mL

Table 3. Summary of equivalence points B. Blank Determination pH V(mL) ΔpH ΔV(mL) ΔpH/ΔV Δ(ΔpH/Δvol) Δ(ΔpH/Δvol)/Δvol 12.9 0 -0.02 2 -0.01 12.88 2 -0.01 -0.005 -0.04 2 -0.02 12.84 4 0 0.015 0.0075 -0.01 2 -0.005 12.83 6 0 -0.055 -0.0275 -0.12 2 -0.06 12.71 8 0 0.055 0.0275 -0.01 2 -0.005 12.7 10 0 -0.02 -0.01 -0.05 2 -0.025 12.65 12 0 0.01 0.005 -0.03 2 -0.015 12.62 14 0 -0.005 -0.0025 -0.04 2 -0.02 12.58 16 0 -0.01 -0.005 -0.06 2 -0.03 12.52 18 0 -0.035 -0.0175 -0.13 2 -0.065 12.39 20 0 -0.01 -0.005 -0.15 2 -0.075 12.24 22 0 -0.075 -0.0375 -0.3 2 -0.15 11.94 24 -0.845 -0.4225 -1.99 2 -0.995 9.95 26 -2.56 -1.28 -7.11 2 -3.555 2.84 28 3.165 1.5825 -0.78 2 -0.39 2.06 30 0.28 0.14 -0.22 2 -0.11 Table 4. Back titration data for exploratory titration

14

12

10

9.95

8

6 pH vs vol 4

First derivative

2.84

Second Derivative

2 1.5825

0 0

5

10

15

20

-2

30

35

-1.28 -3.555

-4

-6

25

ΔVolume of 0.5 N HCl VS (mL)

Figure 5. Overall graphical presentation for the pH curve (blue), first derivative curve (red), and second derivative curve (green) for the exploratory titration of the blank determination

In the pH curve, the equivalence point of the titration is very visible in the curve. The volume consumed at the first equivalence point is approximately 26.00 mL and 28.00 mL for the second equivalence point. In the first derivative curve, it is shown that at 28.00 mL, the sign of the first derivative changed, resulting to the formation of the minimum point of the graph, which is -3.555. From the graph at point -3.555, one can see that the slope changed which indicates that the point would be a possible endpoint. In the second derivative curve, the minimum and maximum points before and after zero is 26 and 28. The point where 0 would have a y-value in between the points before and after zero would indicate a possible endpoint. The y value of 1.5825 coincided with the x-axis at 28.00 mL. This implies the equivalence point of the titration. EXPLORATORY TITRATION pH CURVE 1st Equivalence Point 26.00 mL (9.95pH) 2nd Equivalence Point 28.00 mL (2.84 pH) FIRST DERIVATIVE Equivalence Point 28.00 mL (-3.555 pH) SECOND DERIVATIVE Equivalence Point 28.00 mL (1.5825 pH) Table 5. Summary of equivalence points in the blank determination VIII. Post-Lab Computations A. Endpoint a) Actual Titration

𝐸𝑛𝑑𝑝𝑜𝑖𝑛𝑡 (𝐸𝑉) = 17.50 𝑚𝐿 +

−3.84 𝑥 0.5 −3.84 − 3.56

EV = 17.7595 mL b) Blank Determination

c) 𝐸𝑛𝑑𝑝𝑜𝑖𝑛𝑡 (𝐸𝑉) = 27.00 𝑚𝐿 +

−1.28 −1.28−1.5825

𝑥 0.1

EV = 27.4472 mL B. Percentage Purity a) Monobasic Sodium Phosphate |0.5 𝑁 𝑥 0.5203 𝑥 (28.00 𝑚𝐿 − 4.00 𝑚𝐿)𝑥 %𝑃 =

0.069 𝑔

119.98 𝑔/𝑚𝑜𝑙 1,000 𝑥 2

|

%P = 5.4283 g b) Dibasic Sodium Phosphate |0.5 𝑁 𝑥 0.5203 𝑥 (17.50 𝑚𝐿 − 28.00 𝑚𝐿)𝑥 %𝑃 =

141.96 𝑔/𝑚𝑜𝑙 1,000 𝑥 1

|

0.134 𝑔 %P = 2.8938 g

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ThermoFisher Scientific. (2006, September 8). Sodium Phosphate Material Safety Data Sheet[PDF]. Waltham: Thermo Fisher Scientific.