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PHARMACEUTICAL ANALYSIS I

MIDTERM TABULATION

Submitted by:
Aranzanso, Jhesanne V.
Buenviaje, Yodgh
Butao, Carla Antonette
Javier, Arjielene L.
Miranda, Andrea Ray T.
Montes, Sat Gian Carlos Manuel C.
NEUTRALIZATION ASSAYS

1. Aromatic Spirit of Ammonia (for NH3)


2. Aromatic Spirit of Ammonia (for Ammonium Carbonate)
3. Sodium Bicarbonate Tablets
4. Sodium Borate
5. Sodium Hydroxide (Total Alkali)
6. Sodium Hydroxide (Carbonate Content)
7. Aspirin
8. Aspirin Capsules (old assay in Jenkins)
9. Benzyl Benzoate
10. Boric Acid
11. Ethyl Acetate
12. Potassium Sodium Tartrate
13. Dilute Phosphoric Acid
14. Sodium Tartrate
15. Tretinoin
16. Zinc Oxide and Salicylic Acid Paste (for Salicylic Acid)
ASSAY OF AROMATIC SPIRIT OF AMMONIA (NH3 Content)
Analyte Aromatic Spirit of Ammonia (for NH3)
Official Requirement Aromatic Ammonia Spirit is a hydroalcoholic solution that contains, in each 100 mL,
not less than 1.7g and not more than 2.1 g total of NH3, and Ammonium Carbonate
corresponding to not less than 3.5 g and not more than 4.5 g of (NH4)2CO3.
Volumetric Solution/s Used Back: 0.5 N Sodium Hydroxide VS
Excess: 0.5 N Sulfuric Acid VS
Blank: 0.5 N Sulfuric Acid VS
Type of Assay Neutralization
Type of Titration Residual with Blank Determination
Indicator Used Methyl Red TS
Color Transition at Endpoint Colorless to Pale Yellow
Chemical Reactions Involved 2NH3 + H2SO4⟶ (NH4)2SO4
(NH4)2SO4 + 2NaOH ⟶ Na2SO4 + 2NH3 + 2H2O
(NH4)2CO3 + H2SO4⟶ (NH4)2SO4 + H2O + CO2
Factor used in the Assay f=1
Formula in Computing the P% and LC%
RFIS 1. Boil the test compound to help evaporate the alcohol content in the spirit.
2. Perform a blank determination to determine the amount of other substances
present in the mixture.
ASSAY OF AROMATIC SPIRIT OF AMMONIA (Carbonate Content)
Analyte Aromatic Spirit of Ammonia (for Ammonium Carbonate)
Official Requirement Aromatic Ammonia Spirit is a hydroalcoholic solution that contains, in each 100 mL,
not less than 1.7g and not more than 2.1 g total of NH3, and Ammonium Carbonate
corresponding to not less than 3.5 g and not more than 4.5 g of (NH4)2CO3
Volumetric Solution/s Used 0.5 N Sulfuric Acid VS
Type of Assay Neutralization
Type of Titration Indirect Titration with Blank Determination
Indicator Used Phenolphthalein TS; Methyl Orange TS
Color Transition at Endpoint Faint Pink to Colorless; Orange to Pale Yellow
Chemical Reactions Involved 1. Liberation of ammonia
(NH4)2CO3 + 2NaOH ⟶ 2NH3 ↑ + 2 H2O + Na2CO3

2. Phenolphthalein endpoint
2Na2CO3 + H2SO4 ⟶ 2NaHCO3 + Na2SO4
2NaOH + H2SO4 ⟶ Na2SO4 + 2 H2O
Na2CO3 + NaOH + H2SO4 → NaHCO3 + H2O + Na2SO4

3. Methyl orange endpoint


2NaHCO3 + H2SO4 ⟶ Na2SO4 + 2 H2O + 2CO2 ↑

4. Overall equation
2Na2CO3 + 2H2SO4 ⟶ Na2SO4 + 2H2O + 2CO2 ↑
Factor used in the Assay f = 2 because only 2 moles of H+ ions were transferred in the reactions.
Formula in Computing the P% and LC%
RFIS 1. Aromatic spirit of ammonia must be stored away from light. if exposed to
light, it may result to a lower percentage of alcohol concentration. The active
ingredient of Aromatic spirit of ammonia which is ammonium carbonate, is volatile
at room temperature. It releases ammonia and carbon dioxide when exposed to
air.
2. Add excess NaOH. This is done to ensure the liberation of ammonia and to
make the ammonium salts more basic.
3. Boil the mixture until the vapors no longer turn moistened red litmus
paper to blue. This is done to expel ammonia from the solution and to ensure
completion of reaction. Boiling can affect the progression of reaction of sodium
hydroxide with ammonium carbonate due to the presence of ammonia - which
can react with water to form ammonium hydroxide. Increase in ammonium ion
present in the solution may hinder the previous reaction by virtue of Le
Chatelier’s principles. With this, it might affect the results by decreasing amount
of titrant used since there is a decrease in the production of sodium carbonate.
4. Cool, dilute, with 100 mL of cold, carbon dioxide-free water. This is done
to prevent the formation of a sodium bicarbonate precipitate. Not using carbon
dioxide-free water will accumulate to less volume of titrant consumed.
5. Add 6 drops of phenolphthalein TS to determine the phenolphthalein
endpoint which indicates the neutralization of sodium carbonate to bicarbonate
and sodium hydroxide to sodium sulfate.
6. Add methyl orange TS. The presence of the methyl orange indicator will
result in the neutralization of sodium bicarbonate to carbonic acid and the
production of carbon dioxide and water.
7. Perform a blank determination to determine how much sodium hydroxide
will react with the titrant. Not performing a blank determination will result in a
falsely high percentage of alcohol.
ASSAY OF SODIUM BICARBONATE TABLETS
Analyte Sodium Bicarbonate Tablets
Official Requirement Sodium bicarbonate tablets contain not less than 95.0% and not more than 105.0% of
the labelled amount of NaHCO3
Volumetric Solution/s Used 1 N Hydrochloric Acid
Type of Assay Neutralization
Type of Titration Direct without Blank Determination
Indicator Used Methyl Red TS
Color Transition at Endpoint Yellow – Peach color
Chemical Reactions Involved NaHCO3 + HCl → NaCl + H2O+ CO2
Factor used in the Assay f = 1 because only 1 replaceable H+ is involved in the neutralization
Formula in Computing the P% and LC% 0.1 𝑁 𝑥 𝑁𝐹𝐻𝐶𝑙 𝑥 𝑉𝐻𝐶𝑙 𝑥 1,000 𝑥 1
𝑀𝑊
%𝐿𝐶 =
𝐿𝐶
𝑤𝑡 𝑠𝑎𝑚𝑝𝑙𝑒 𝑥
𝑎𝑣𝑒. 𝑤𝑡/𝑡𝑎𝑏

RFIS 1. Weighing of NLT 20 tablets, for better representation of the whole batch of
the tablet . Also, according to USP, the minimum number needed to get the
average weight of the tablets is 20.
2. Finely powdered tablets. Increased surface area leads to faster dissolution
and faster reaction with HCl.
3. Dissolution of tablets. Dissolution of tablets in water is performed because in
its dry, solid state it does not react with acids.
4. Methyl red as indicator. Unlike other indicators, methyl red is not affected by
the carbonic acid liberated in the reaction. Neutralization of sodium
bicarbonate
(weak base) by hydrochloric acid (strong acid) results to a slightly acidic
solution.
5. Boiling destroys the HCO3/CO2 buffer system and to liberate the carbon
dioxide
formed in the reaction. Endpoint becomes sharper.
6. Add HCl slowly to help prevent rapid heat generation and splattering of the
mixture.
7. Heat the solution to boiling then cool because the carbonic acid produced
as a result of these titrations can decompose into carbon dioxide.
ASSAY OF SODIUM BORATE
Analyte Sodium Borate
Official Requirement Sodium borate contains an amount of Na2B4O7 equivalent to not less than 99.0
percent and not more than 105.0 percent of Na2B4O7 * 5H2O.
Volumetric Solution/s Used 0.5 N Hydrochloric Acid
Type of Assay Neutralization
Type of Titration Direct with Blank Determination
Indicator Used Methyl Red TS
Color Transition at Endpoint Yellow – Peach color
Chemical Reactions Involved Na2B4O7 * 10H2O + 2HCl ⟶ 4H3BO3 + 2NaCl + 5H2O
Factor used in the Assay f = 2 because 2 moles of HCl will react with Na2B4O7 * 10H2O
Formula in Computing the P% and LC% 0.5 𝑁 𝑋 𝑁𝐹 𝑋 𝑉𝐻𝐶𝑙 𝑥
381.17 𝑔/𝑚𝑜𝑙
1,000 𝑥 2
%𝑃 = 𝑥 100
𝑤𝑡 𝑠𝑎𝑚𝑝𝑙𝑒
RFIS 1. ...add methyl red TS. Methyl red TS is used in this assay as the indicator
because it is not affected by a weak protic acid, like boric acid, producing a
sharp endpoint at room temperature.
2. ...and titrate with 0.5 N HCl. A strong acid, HCl, is used in this assay because
it reacts completely with the analyte (Skoog, 2013).
3. Boiling of water is initially done to remove carbon dioxide present and for
faster dissolution of sodium borate.
ASSAY OF SODIUM HYDROXIDE (TOTAL ALKALI)
Analyte Sodium Hydroxide
Official Requirement Potassium Hydroxide contains NLT 85% of total alkali, calculated as KOH, including
NMT 3.5% of Potassium Carbonate.
Volumetric Solution/s Used 1 N Sulfuric Acid
Type of Assay Neutralization
Type of Titration Double Direct
Indicator Used Phenolphthalein TS; Methyl Orange TS
Color Transition at Endpoint Pink to Colorless; Orange to Peach
Chemical Reactions Involved 1. Phenolphthalein endpoint
2NaOH + H2SO4⟶ Na2SO4 + 2H2O
NaOH + H2SO4 ⟶ NaHSO4 + H2O (fully neutralized)
Na2CO3 + H2SO4⟶ Na2SO4 + NaHCO3

2. Methyl orange endpoint


NaHCO3 + H2SO4⟶ NaHSO4 + CO2 + H2O
Factor used in the Assay f = 1 because there is 1 mole of NaOH that reacts with 1 mole of H2SO4.
Formula in Computing the P% and LC%
RFIS 1. Boil the water for 30 minutes to remove CO2 in the solution.
2. Cool the solution to increase the solubility of NaOH and to not affect the
calibration of burette when vapors of hot solution rise.
3. Two indicators were used to detect basic endpoint by adding
phenolphthalein and to detect acidic endpoint by adding methyl orange.
 Phenolphthalein TS is added to half neutralize Na2CO3 to NaHCO3.
 Methyl Orange TS is added to fully neutralize Na2CO3 to NaHCO3.
ASSAY OF SODIUM HYDROXIDE (CARBONATE CONTENT
Analyte Sodium Hydroxide
Official Requirement Potassium Hydroxide contains NLT 85% of total alkali, calculated as KOH, including
NMT 3.5% of Potassium Carbonate.
Volumetric Solution/s Used 1 N Sulfuric Acid
Type of Assay Neutralization
Type of Titration Double Direct Titration
Indicator Used Phenolphthalein TS; Methyl Orange TS
Color Transition at Endpoint Pink to Colorless; Orange to Peach
Chemical Reactions Involved 1. Phenolphthalein endpoint

NaOH + H2SO4 ⟶NaHSO4 + H2O


Na2CO3 + H2SO4⟶ NaHSO4 + KHCO3

2. Methyl orange endpoint

NaHCO3 + H2SO4⟶ NaHSO4 + CO2 + H2O


Na2CO3 + H2O ⟶ 2NaOH + CO2
Factor used in the Assay f = 2 because 2 moles of OH- reacted with 1 mole of CO32-.
Formula in Computing the P% and LC%
RFIS 1. Use carbon dioxide free water to remove CO2 which can produce sodium
carbonate when carbon dioxide reacts with NaOH and to prevent the
accumulation of carbonate content of the strong alkali. Boil water for 30 minutes
to obtain carbon dioxide free water.
2. Cool the recently boiled water to 15 Co. Using hot water will only solidify
NaOH. To easily solubilize NaOH dissolve it in cold water because the dissolution
of KOH is exothermic.
3. Two indicators were used to detect basic endpoint by adding
phenolphthalein and to detect acidic endpoint by adding methyl orange.
 Phenolphthalein TS is added to half neutralize Na2CO3 to NaHCO3.
 Methyl Orange TS is added to fully neutralize Na2CO3 to NaHCO3. Also it
is not affected by CO2.
ASSAY OF ASPIRIN
Analyte Aspirin
Official Requirement Aspirin contains NLT 99.5% and NMT 100.5% of Aspirin
Volumetric Solution/s Used Back Titrant: 0.5 N Sulfuric Acid VS
Excess Titrant: 0.5 N Sodium Hydroxide VS
Type of Assay Alkalimetry
Type of Titration Residual Titration with Blank Determination
Indicator Used Phenolphthalein TS
Color Transition at Endpoint Pink to Colorless
Chemical Reactions Involved 1. Sponification of aspirin

2. Hydrolysis:
Factor used in the Assay 2, because 1 mole of H+ ion is needed to react with 2 moles of OH-
Formula in Computing the P% and LC%
RFIS 1. Add 50.0 mL of 0.5 N NaOH VS. After neutralizing its hydrolysis
products, the addition of excess NaOH saponifies aspirin.
2. Acetylsalicylic acid is titrated with NaOH. Neutralizing any free acid
formed by the hydrolysis of acetylsalicylic acid.
3. Boil the mixture gently for 10 minutes. To create a chemical reaction,
boiling the mixture will completely dissolve aspirin in NaOh.
4. Back titrate with 0.1 N H2SO4. H2SO4 titrates back excess NaOH that
did not react in the saponification process .HCl releases chloride ions
that can react in aspirin with salicylic acid, producing by product
unwanted, thus using H2SO4.
ASSAY OF ASPIRIN (old assay)
Analyte Aspirin Capsules
Official Requirement Aspirin Tablets contain not less than 90% and not more than 110.0% of the labeled
amount of Aspirin.
Volumetric Solution/s Used Back Titrant: 0.1 N Sulfuric Acid
Excess Titrant: 0.5 N Sodium Hydroxide VS
Type of Assay Alkalimetry
Type of Titration Residual with Blank Determination
Indicator Used Phenolphthalein TS
Color Transition at Endpoint Colorless to Pink
Chemical Reactions Involved 1. Neutralization of aspirin with NaOH

2. Back Titration with 0.1 N H2SO4

2NaOH + H2SO4 ⟶ Na2SO4 + 2H2O

OH f = 1, because 1 H+ ion was displaced by NaOH in the neutralization rection.


Formula in Computing the P% and LC%
RFIS 1. Weigh and powder not less than 20 Aspirin tablets. As the potency of
the final product is based on the average of 20 dosage units, no less
than 20 tablets are to be used.
2. Transfer the sample to an Erlenmeyer flask with the aid of 20 mL
neutralized alcohol. Aspirin is more soluble in alcohol than water,
alcohol is used. Alcohol cooling is done to avoid evaporation as alcohol
is a volatile substance.
3. Add Phenolphthalein and titrate with with 0.1 N NaOH. NaOH
neutralizes hydrolysis - forming free acids as well as the acetylsalicylic
acid carboxyl group. Phenolphthalein is used as an indicator because
the process of titration is between a weak acidand a strong base.
4. Heat the mixture in boiling water bath for 15 minutes. Heating
accelerates the reaction and makes saponification easier.
5. Perform blank determination. Corrects any factors, which may have
contributed to the inaccuracy of the volumes of the titrants.
ASSAY OF BENZYL BENZOATE
Analyte Benzyl Benzoate
Official Requirement Benzyl Benzoate contains not less than 99.0% and not more than 100.5% of
C14H12O2.
Volumetric Solution/s Used Back Titrant: 0.5 N Hydrochloric Acid
Excess Titrant: 0.5 N Alcoholic Potassium Hydroxide VS
Type of Assay Acidimetry
Type of Titration Residual with Blank Determination
Indicator Used Phenolphthalein TS
Color Transition at Endpoint Pink to Colorless
Chemical Reactions Involved

Factor used in the Assay Factor is 1, because 1 mole of benzyl benzoate is needed to react with 1 mole of NaOH
Formula in Computing the P% and LC%
RFIS 1. Add 50.0 mL of 0.5 N alcoholic potassium hydroxide VS. To completely
solubulize water-insoluble benzyl benzoate
2. Boil. To saponify
3. Titrate with 0.5 N hydrochloric acid VS. Alcoholic KOH will react with
sulfuric acid and will produce potassium sulfate precipitate.
ASSAY OF BORIC ACID
Analyte Boric Acid
Official Requirement Boric Acid contains NLT 99.5% and NMT 100.5% of H3BO3.
Volumetric Solution/s Used 1N NaOH VS
Type of Assay Alkalimetry
Type of Titration Direct Titration
Indicator Used Phenolphthalein TS
Color Transition at Endpoint Clear to Pale Pink
Chemical Reactions Involved

Factor used in the Assay Factor is 1, because there is 1 replaceable H+ that reacts with 1 mole of NaOH
Formula in Computing the P% and LC%
RFIS 1. Dissolve in 100 mL of a mixture of equal volumes of glycerin and
water. Boric Acid is freely soluble in glycerin and water. Boric Acid with
glycerin forms a glyceryl-boric formation which acts as a strong acid that
creates interaction with the titrant 1 N sodium hydroxide.
2. ...previously neutralized with phenolphthalein. To prevent acidic pH
of glycerine-water complex due to contribution of H+. Also, boric acid acts
as an acid to phenolphthalein. It can be qualitatively titrated in the
presence of polyhydroxy compound such as glycerol, which prevents the
hydrolysis of sodium borate.
3. Titrate with 1 N Sodium Hydroxide VS: To neutralize glycerine.
ASSAY OF ETHYL ACETATE
Analyte Ethyl Acetate
Official Requirement Ethyl Acetate contains NLT 99% and NMT 100.5% of Ethyl Acetate
Volumetric Solution/s Used Back Titrant: 0.5 N Hydrochloric Acid VS
Excess Ttitrant: 0.5N Sodium Hydroxide
Blank: 0.5N Sodium Hydroxide
Type of Assay Acidimetry
Type of Titration Residual with Blank Determination
Indicator Used Phenolphthalein TS
Color Transition at Endpoint Pink to Colorless
Chemical Reactions Involved 1. Esterification of ethyl acetate

2. Blank determination with 0.5 N NaOH

NaOH + HCl ⟶ NaCl + H2O

Factor used in the Assay f = 1 because there is 1 replaceable H+ from 1 mole of HCl that will react with 1 mole of NaOH.
Formula in Computing the P%
and LC%
RFIS 1. Weigh 1.5 g of Ethyl Acetate in a stoppered weighing bottle. Ethyl Acetate is volatilized
even at low temperatures.
2. Naturally, esters can not be titrated directly due to their slow reactivity, thus residual titration
is performed. Since the base ester reaction is slow, it is necessary to add excess alkali before
saponifying under a reflux condenser.
3. The saponification of ethyl acetate is done by heating under a reflux condenser for 1
hour. Sodium acetate and ethanol are produced by alkaline hydrolysis of ethyl acetate and
sodium hydroxide. The reaction is essentially irreversible, as there is little tendency to react
with alcohol in a resonance - stabilized carboxylate anion.
4. Perform a blank determination. Under the same conditions as the actual test, the blank test
corrects any factors that may have contributed to the inaccuracy of the volume of the titrant,
such as the incomplete saponification of ethyl acetate and phenolphthalein.
ASSAY OF POTASSIUM SODIUM TARTRATE
Analyte Sodium Tartrate
Official Requirement Sodium Tartrate contains NLT 99.0% and NMT 102.0% of C4H4KnaO6, calculated on
the anhydrous basis.
Volumetric Solution/s Used Back Titrant: 0.5 N Sodium Hydroxide VS
Excess Titrant: 0.5 N Sulfuric Acid VS
Type of Assay Acidimetry
Type of Titration Residual Titration with Blank determination
Indicator Used Methyl Red-Methylene Blue
Color Transition at Endpoint Red-violet to Blue
Chemical Reactions Involved 1. Ignition of salt
C4H4KnaO6 KNaCO3

2. Reaction of KnaCO3 with H2SO4


KNaCO3 + H2SO4 ⟶ KNaSO4 + H2O + CO2
Factor used in the Assay f = 2, because there are 2 replaceable hydrogen per 1 mole of sulfuric acid.
Formula in Computing the P% and LC%
RFIS 1. Weigh accurately about 2 g of potassium sodium tartrate in a tared
porcelain crucible and ignite, gently at first until the salt is thoroughly
carbonized. The salt is heated slowly at first, since the sample swells and
fuses with concomitant decomposition. If strong heat is applied In the initial
stages of ignition, there may be loss of a portion of the sample through
decrepitation or splattering. After the mass in the crucible is partially charred
and white fumes are no longer evolved, it is ignited to dull redness. If heated
too strongly or if the flame comes in contact with the carbonized mass, the
alkali carbonate may be converted into the oxide.
2. Cool the crucible, place it in a glass beaker, and break up the carbonized
mass with a glass rod. The fused residue is broken up by means of a strong
glass rod over glazed, black paper and transferred with the crucible into a 250
mL beaker.
3. …add 50 mL of water and 50. 0 mL of 0.5 N Sulfuric Acid VS. 0.5 N
Sulfuric Acid VS Is added to completely oxidize all carbons. Also completely
dissolve the mass.
4. And boil the solution for 30 minutes. To facilitate the reaction while
removing CO2 formed as a by product.
5. Filter and wash with hot water until the last washing is neutral to
lithmus. Hot water is used instead of cold water for the tartrate to stay on its
crystal form, not amorphous form.
6. Add merthyl red-methylene blue TS. It is used since the boiling process rids
the solution of any carbon dioxide which otherwise would affect the
equivalence point of the titration.
7. Perform a blank determination. The blank test is carried out under the same
conditions as the actual test, corrects any factors that might have contributed
to inaccuracy of the titrant’s volume.
ASSAY OF DILUTE PHOSPORIC ACID
Analyte Dilute Phosphoric Acid
Official Requirement Dilute Phosphoric Acid contains, in each 100 mL, NLT 9.5 g and NMT 10.5 g of
Phosphoric Acid.
Volumetric Solution/s Used 1 N Sodium Hydroxide
Type of Assay Neutralization
Type of Titration Direct with Blank Determination
Indicator Used Thymolphthalein
Color Transition at Endpoint Colorless to Pale Blue
Chemical Reactions Involved 1. Reaction between phosphoric acid and sodium hydroxide

H3PO4 + 2NaOH⟶2NaH2PO4 + H2O


NaH2PO4 +NaOH⟶Na2HPO4 +H2O
H3PO4 +3NaOH⟶Na2HPO4 + H2O
Factor used in the Assay f = 2 because there are 2 replacable H+ ions in 1 mole of Phosphoric Acid
Formula in Computing the P% and LC%
RFIS 1. Add 0.5 mL of thymolphthalein TS. The pH range for the color change of
thymolphthalein is 9.3 - 10.5. This may have been chosen as the indicator for
the reaction instead of other indicators since the color change involved here
may occur closer to the equivalence point as compared to other indicators.
2. Perform a blank determination. A blank determination is run if there is a
reason to believe that the reagents in the official procedure or the conditions
under which the analysis is performed may interfere or compete with the titrant
or complement the titrant. In this analysis, the indicator changes color in a very
basic range, and consequently any volume of sodium hydroxide used in the
blank to bring about the color change must be accounted for the actual
analysis.
ASSAY OF SODIUM TARTRATE
Analyte Sodium Tartrate
Official Requirement Sodium Tartrate contains NLT 99.0% and NMT 100.5% of C4H4Na2O62H2O
calculated on a dried basis.
Volumetric Solution/s Used 0.1 N Perchloric Acid VS
Type of Assay Potentiometry
Type of Titration Direct Titration with Blank determination
Indicator Used Potentiometric endpoint through pH
Color Transition at Endpoint None
Chemical Reactions Involved
Factor used in the Assay
Formula in Computing the P% and LC%
RFIS 1. Transfer about 250 mg of sodium tartrate, accurately weighed and
previously dried at 150 degress for 3 hours. Sodium tartrate has water of
hydration. It is dried to remove its moisture content.
2. Dissolve by stirring or heating to near boiling point in 150 mL acetic
acid.
3. Titrate with 0.1 N Perchloric Acid VS ( in glacial acetic acid)
4. Determine the endpoint potientiometrically.
5. Perform a blank determination.
ASSAY OF TRETINOIN
Analyte Tretinoin
Official Requirement Tretinoin contains not less than 97.0 percent and not more than 103.0 percent of
C20H28O2on dried basis
Volumetric Solution/s Used 0.1 N Sodium Methoxide
Type of Assay Neutralization Assay
Type of Titration Direct with Blank Determination
Indicator Used Thymol Blue
Color Transition at Endpoint Yellow to green
Chemical Reactions Involved
Factor used in the Assay
Formula in Computing the P% and LC%
RFIS 1. Dimethylformamide
Tretinoin is soluble in organic solvents such as dimethylformamide
2. Add 3 drops of 1 in 100 solution of thymol blue in dimethylformamide
3. 0.1 N Sodium Methoxide VS
Sodium methoxide is a strong base
ASSAY OF ZINC OXIDE AND SALICYLIC ACID PASTE (FOR SALICYLIC ACID)
Analyte Salicylic Acid
Official Requirement Zinc Oxide and Salicylic Pate contains not less than 23.5 percent and not more than
25.5 percent of zinc oxide, and not less than 1.9 percent and not more than 2.1 percent of
salicylic acid.
Volumetric Solution/s Used
Type of Assay
Type of Titration
Indicator Used Phenol red
Color Transition at Endpoint
Chemical Reactions Involved
Factor used in the Assay
Formula in Computing the P% and LC% 𝑁 𝑁𝑎𝑂𝐻𝑥 𝑁𝐹𝑁𝑎𝑂𝐻 𝑥 𝑉𝑁𝑎𝑂𝐻𝑥
𝑀𝑊 𝑆𝑎𝑙𝑖𝑐𝑦𝑙𝑖𝑐 𝐴𝑐𝑖𝑑
%P = 1 𝑥 1000
𝑤𝑡 𝑠𝑎𝑚𝑝𝑙𝑒
RFIS 1. Add 40 ml alcohol
2. Alcohol previously neutralized with 0.1 N sodium hydroxide
3. Phenol red
4. Heat on water bath with frequent swirling
REDOX ASSAYS
1. Antimony Potassium Tartrate
2. Ascorbic Acid
3. Ascorbic Acid Tablets
4. Ferrous Sulfate Tablets
5. Hydrogen Peroxide Topical Solution
6. Iodine Topical Solution (for I2)
7. Iodine Topical Solution (for NaI)
8. Sodium Formaldehyde Sulfoxylate
9. Sodium Iodide
10. Sodium Metabisulfite
11. Sodium Nitrite Injection
12. Sodium Thiosulfate Injection
13. Sulfur Dioxide
14. Thymol
15. Titanium Dioxide
ASSAY OF ANTIMONY POTASSIUM TARTRATE
Analyte antimony potassium tartrate
Official Requirement Antimony Potassium Tartrate contains not less than 99.0 percent and not more than
103.0 percent of C8H4K2O12Sb2·3H2O.
Volumetric Solution/s Used 0.1N iodine VS
Type of Assay Iodimetry
Type of Titration Direct
Indicator Used Starch TS
Color Transition at Endpoint Colorless to persistent blue color
Chemical Reactions Involved 1. Reaction of Antimony Potassium Tartrate to Iodine:
Half reactions:
Oxidation: I2 + 2e- → 2I-
Reduction: SbO+ + H2O → SbO2+ + 2H+ + 2e-
I2 + SbO+ + H2O → SbO2 + 2H+ + 2I-
Net Ionic Balanced Eq.: 2I2 + C8H4K2O10(SbO)2 + 2H2O → 4HI + C8H4K2O10(SbO2)2

2. Reaction of Hydriodic Acid and Sodium Borate:


2HI + Na2B4O7 + 5H2O → 2NaI + 4H3BO3
Factor used in the Assay f=4

Formula in Computing the P% and LC% 667.87 𝑔/𝑚𝑜𝑙


0.1 𝑁 𝑥 𝑁𝐹𝑖𝑜𝑑𝑖𝑛𝑒 𝑉𝑆 𝑥 𝑉𝑖𝑜𝑑𝑖𝑛𝑒 𝑉𝑆 𝑥 1,000 𝑥 4
%𝑃 = 𝑥 100
𝑤𝑡 𝑠𝑎𝑚𝑝𝑙𝑒
RFIS 1. ...add 5 g of potassium sodium tartrate. Potassium sodium tartrate is added to
prevent the precipitation of basic salts of antimony by hydrolysis. Precipitated salt
of antimony would no longer be able to participate in the titration, thus the results
of the assay will be compromised.
2. ...2 g of sodium borate. Sodium Borate is added as a buffer to maintain the
solution’s alkalinity. It must be considered that the titration must be carried out in
an alkaline condition for this assay because of these reasons:
 The indicator used in this assay, starch, tends to hydrolyze or decompose in acidic
medium, thus, the end point may be affected.
 The pH of the solution affects the reduction potential of the trivalent antimony.

KOOCCHOHCHOCHOHCOO(SbO) + I2+ H2O KOOCCHOHCHOHCOO(SbO2) + 2H+ + 2I+

 Based on the equation above, if the H+ concentration is high, the equilibrium will
shift to the left. Therefore, employing an alkaline solution will prevent the left shift
of the reaction by neutralizing the hydrogen ions.
 The iodide ions produced in the reaction tends to be oxidized by dissolved oxygen
in the acid solution.
4I- + O2 + H+ 2I2 + H2O

 Since in an alkaline medium, the hydrogen ions are neutralized, there will be no
hydrogen ions to participate in the reaction above.
3. ...3 mL of starch TS. Starch is the indicator used in this assay because when all
the trivalent antimony have been oxidized to pentavalent antimony, iodine will
consequently not be reduced to iodide and starch will be able to absorb iodine,
forming a persistently blue colored solution.
4. ...and immediately titrate. Starch must be immediately titrated with the analyte
because it can be easily biodegraded.
5. ... titrate with 0.1N iodine VS. 0.1N Iodine VS is the titrant due to its moderately
strong oxidizing property.
ASSAY OF ASCORBIC ACID TABLETS
Analyte Ascorbic Acid tablets
Official Requirement Ascorbic Acid Tablet contain NLT 90.0% and NMT 110.0% of the labeled amount of
ascorbic acid (C6H8O6).
Volumetric Solution/s Used dichlorophenol-indophenol VS
Type of Assay Permanganometry
Type of Titration Direct titration with blank determination
Indicator Used dichlorophenol-indophenol VS
Color Transition at Endpoint Colorless to Rose-pink
Chemical Reactions Involved

Factor used in the Assay f=2


Formula in Computing the P% and LC% 𝑀𝑊
𝑁 𝑋 𝑁𝐹𝐾𝑀𝑛𝑂4 𝑉𝑆 𝑋 (𝑉𝑎𝑐𝑡𝑢𝑎𝑙 − 𝑉𝑏𝑙𝑎𝑛𝑘)𝑥 1,000 𝑋 2
%𝑃 = 𝑥 100
𝑠𝑎𝑚𝑝𝑙𝑒 𝑤𝑡
RFIS 1. No indicator is necessary, since the oxidized form of the dichlorophenol-
indophenol is blue in alkali and red in acid, while the reduced form is colorless.
2. Perform blank determination. Whenever there is reason to believe that the
reagents in the official procedure or the conditions under which the analysis is
performed may interfere or compete for the titrant or complement the titrant, a
blank determination is run so that any of the possible interference may be
appropriately corrected for.
ASSAY OF FERROUS SULFATE TABLETS
Analyte Ferrous sulfate
Official Requirement Ferrous sulfate tablets contain not less than 95.0 percent and not more than 110.0
percent of the labeled amount of ferrous sulfate
Volumetric Solution/s Used 0.1 N Ceric Sulfate
Type of Assay Redox Assay
Type of Titration Direct Titration
Indicator Used Orthophenanthrolin TS
Color Transition at Endpoint Red to faint blue
Chemical Reactions Involved 1. Redox reaction between ferrous sulfate and ceric sulfate
Half reactions:
Oxidation: Fe2+ ⇌ Fe3+ + e-
Reduction : Ce4+ + e- ⇌ Ce3+
Fe2+ + Ce4+ → Fe3+ + Ce3+
Net Ionic Balanced Eq.: 2FeSO4 + 2Ce(SO4)2→ Fe2(SO4)3 + Ce2(SO4)3

Factor used in the Assay f=1


Formula in Computing the P% and LC% 𝑁𝐶𝑒(𝑆𝑂4)2 𝑥 𝑁𝐹𝐶𝑒(𝑆𝑂4)2 𝑥 𝑉𝐶𝑒(𝑆𝑂4)2 𝑥
𝑚𝑤 𝐹𝑒𝑆𝑂4
1 𝑥 1000
%P=
𝑤𝑡 𝑠𝑎𝑚𝑝𝑙𝑒

𝑚𝑤 𝐹𝑒𝑆𝑂4
𝑁𝐶𝑒(𝑆𝑂4)2 𝑥 𝑁𝐹𝐶𝑒(𝑆𝑂4)2 𝑥 𝐶𝑒(𝑆𝑂4)2 𝑥
1 𝑥 1000
%LC = 𝑙𝑎𝑏𝑒𝑙𝑒𝑑 𝑎𝑚𝑜𝑢𝑛𝑡
𝑤𝑡 𝑝𝑜𝑤𝑑𝑒𝑟𝑒𝑑 𝑡𝑎𝑏𝑙𝑒𝑡 𝑥
𝑎𝑣𝑒 𝑤𝑡 𝑜𝑓 𝑡𝑎𝑏𝑙𝑒𝑡

RFIS 1. Weigh and finely powder not fewer than 20 tablets. According to USP, the
minimum number needed to get the average weight of the tablets is 20; this
ensures an accurate representation of the tablets. It must be finely powdered
to increase the surface for better dissolution of tablets and for greater
solubility.
2. Dissolve the sample in a mixture of 20 mL of 2 N H2SO4. Ceric sulfate in
diluted sulfuric acid is a strong oxidizing agent and considerably more stable
than standard potassium permanganate. Moreover, Sulfuric acid is added
since solutions of ferrous salts must be kept acidic to prevent air-oxidation of
ferrous ions to ferric state. The rate of oxidation increases as the pH of the
solution increases.
3. ... and 80 mL of freshly boiled and cooled water. Freshly boiled and cooled
water is used to ensure that no carbon dioxide is present in the solution.
Carbonates, which form from reaction of CO2 with water, react readily with
ferrous compounds to precipitate white ferrous carbonate.
4. Filter the solution rapidly as soon as all the soluble ingredients in the
tablet are dissolved.
In addition to medicinal agents, tablets usually contain a number of insoluble
pharmaceutical adjuncts. Filtration is employed to remove these impurities
5. Add Orthophenanthrolin TS. Orthophenathroline is a very satisfactory
indicator in titrations with ceric salts The color of orthophenanthroline changes
from red to [slight blue] when the slightest excess of ceric sulfate is added to
the oxidized solution.
ASSAY OF HYDROGEN PEROXIDE TOPICAL SOLUTION
Analyte Hydrogen Peroxide
Official Requirement Hydrogen Peroxide Topical Solution contains, in each 100 ml, NLT 2.5 g and NMT 3.5
g of hydrogen peroxide. It contains NMT 0.05% of suitable preservative or preservatives.
Volumetric Solution/s Used 0.1 N Potassium Permanganate
Type of Assay Permanganometry
Type of Titration Direct
Indicator Used None (Potassium Permanganate is a self-indicator)
Color Transition at Endpoint Colorless to Faint Pink
Chemical Reactions Involved 1. Redox reaction between potassium permanganate and hydrogen peroxide
Half reactions:
Oxidation: H2O2⟶ O2 + 2H++ 2e-
Reduction: Mno4-+ 8H+ + 5e- ⟶Mn2+ + 4H2O
5H2O2 + 2MnO4−+ 6H+→5O2 + 2Mn2++ 8H2O
Net Ionic Balanced Eq.: 5H2O2 + 2KMnO4− + 3H2SO4→ 5O2 + 2MnSO4+ 8H2O + K2SO4
Factor used in the Assay Hydrogen Peroxide has a factor of 2.
Potassium Permanganate has a factor of 5.
Formula in Computing the P% and LC% g = 0.1 NKMnO4 x NFKMnO4 x VKMno4 x
34.01 𝑔/𝑚𝑜𝑙
2 𝑥 1000

𝑔 𝐻2𝑂2 2.5 𝑔
=
𝑚𝑙 𝐻2𝑂2 100 𝑚𝑙
RFIS 1. The assay requires no indicator as potassium permanganate is used which is
a self-indicator. Since potassium permanganate is heavily colored, the end-
point may be detected when the purple color of the permanganate persists
(Watson p. 73) and the titration must be stopped when the first miniscule trace
of pink color is produced (Dulski, p.150) During a titration with potassium
permanganate, the purple color of the MnO4− is removed as soon as it is added
because it is reduced to Mn2+. As soon as the titration is complete, a fraction of
a drop of excess MnO4 solution imparts a definite pink color to the solution,
indicating that the reaction is complete.
2. Add 20 mL of 2 N Sulfuric Acid. Sulfuric acid is added to maintain a
reasonably constant hydrogen-ion concentration. The addition of sulfuric acid is
needed maintain the acidity of the solution which is necessary for the assay. In
neutral solution, the reduction product of this permanganate is MnO2, rather
than Mn2+ produced in acid medium. The MnO2 acts as a catalyst for further
decomposition of the permanganate, which produces more MnO2, and so on.
The acidic condition of the solution prevents the formation of MnO2 precipitates.
3. … and titrate with 0.1 N Potassium Permanganate VS. Potassium
permanganate is used as a titrant in this assay since it is a stronger oxidizer
than hydrogen peroxide which usually the oxidizing agent. Permanganate in low
pH is strong enough to quantitatively oxidize hydrogen peroxide to oxygen, this
reaction is used for the determination of hydrogen peroxide concentration.
ASSAY OF IODINE TOPICAL SOLUTION (for I2)
Analyte Iodine Topical Solution (for I2)
Official Requirement Iodine Topical Solution contains, in each 100 mL, not less than 1.8 g and not more
than 2.2 g of Iodine (I) and not less than 2.1 g and not more than 2.6 g of Sodium Iodide
(NaI).
Volumetric Solution/s Used 0.1 N Sodium Thiosulfate VS
Type of Assay Iodimetry
Type of Titration Direct Titration
Indicator Used Starch TS
Color Transition at Endpoint Dark Brown to Pale Yellow; Blue to Colorless (upon addition of Starch TS)
Chemical Reactions Involved 1. Reaction of iodine with sodium thiosulfate:
Half reactions:
Reduction: I2 + 2e- → 2I-
Oxidation: 2S2O32- → S4O62-+ 2e-
I2 + S2O32- → 2I- + S4O62-
Net Ionic Balanced Eq.: I2 + 2Na2S2O3 ⟶ 2NaI + Na2S4O6
Factor used in the Assay f = 2 because 2 electrons are lost per iodide ion.
Formula in Computing the P% and LC%
RFIS 1. Transfer 10 mL of Topical Solution into a glass-stoppered, 500-mL flask. A
glass stoppered flask must be used to prevent the escape of iodine gas during
the titration
2. Starch TS is used as the indicator because it is a very sensitive indicator. The
presence of 1 part of iodine is readily detectable in several million parts of the
solution.
3. … adding 3 mL of starch as the endpoint is approached. If starch TS is
added initially, a formation of irreversible starch iodine complex may form and
the detection of endpoint may be hard to discern. It also decomposes
irreversibly at high concentration of iodine.
4. Starch solution must be freshly prepared because it detoriates quickly upon
standing.
ASSAY OF IODINE TOPICAL SOLUTION (for NaI)
Analyte Iodine Topical Solution (for NaI)
Official Requirement Iodine Topical Solution contains, in each 100 mL, not less than 1.8 g and not more
than 2.2 g of Iodine (I) and not less than 2.1 g and not more than 2.6 g of Sodium Iodide
(NaI).
Volumetric Solution/s Used 0.05 M Potassium Iodate VS
Type of Assay Miscellaneous Assay
Type of Titration Direct Titration
Indicator Used Amaranth TS
Color Transition at Endpoint Dark Brown to Pale Brown; Bright Red to Yellow (upon addition of amaranth TS)
Chemical Reactions Involved 1. Formation of I2 upon the reaction of sodium iodide and potassium iodate
Half reactions:
Reduction: 2IO3 + 12H+ + 10e- → I2↑ + 6H2O
-

Oxidation: (2I- → I2↑ + 2e- )5


(2IO3- + 12H+ + 10I- → 6I2↑ + 6H2O)/2
IO3- + 6H+ + 5I- → 3I2↑ + 3H2O
Net Ionic Eq.: 5NaI + KIO3 + 6HCl → 3I2↑ + 5NaCl + KCl + 3H2O

2. Reaction of potassium iodate with I2 to form the interhalogen iodine chloride


Half Reactions:
Reduction: IO3- + 6H+ + 4e- → I+ + 3H2O
Oxidation: (I2 → 2I+ + 2e-)2 .
IO3- + 2I2 + 6H+ → 5I+ + 3H2O
Net Ionic Balanced Eq.: KIO3 + 2I2 + 6HCl → KCl + 5ICl + 2H2O

3. Complete balanced chemical reaction of the assay


(5NaI + KIO3 + 6HCl → 3I2↑ + 5NaCl + KCl + 3H2O)2
(KIO3 + 2I2 + 6HCl → KCl + 5ICl + 3H2O)3
(5NaI + KIO3 + 6HCl → 3I2↑ + 5NaCl + KCl + 3H2O)2
(10NaI + 5KIO3 + 30 HCl → 10NaCl + 5KCl + 15ICl + 15H2O)/5
2NaI + KIO3 + 6HCl → 2NaCl + KCl + 3ICl + 3H2O
Factor used in the Assay f = 2 because 2 electrons are lost per iodide ion.
Formula in Computing the P% and LC%
RFIS 1. Iodine Topical Solution must be titrated away from light because iodine
oxidizes in the presence of light which may cause the solution to become acidic.
2. Transfer 10.0 mL of Topical Solution to a glass-stoppered 500-mL flask. to
prevent air-oxidation of iodine. If not, it will lead to inaccuracy of results.
Therefore, the solution must be kept from becoming too acidic.
3. ...add 30 mL of water and 50 mL of hydrochloric acid. Hydrochloric acid is
added as a catalyst to stabilizes the iodine monochloride to form the HICl2
complex.
4. Add 1 mL of amaranth TS.Amaranth TS is used as the indicator since it is not
affected by highly acidic solutions unlike starch TS which hydrolyses at high pH.
5. Amaranth is added near the endpoint since the temporary excess in the
titrant which usually occurs in the area of addition will gradually decolorize the
indicator before the endpoint is reached. The decolorization of the indicator is
irreversible.
6. The volume of amaranth TS added must be small increments to prevent any
significant indicator error.
ASSAY OF SODIUM IODIDE
Analyte Sodium Iodide
Official Requirement Sodium Iodide contains not less than 99.0 percent and not more than 101.5 percent of
NaI, calculated on the anhydrous basis.
Volumetric Solution/s Used 0.05 M potassium iodate VS
Type of Assay Miscellaneous Assay
Type of Titration Direct titration
Indicator Used amaranth TS
Color Transition at Endpoint Dark Brown to Pale Brown; Bright Red to Yellow (upon addition of amaranth TS)
Chemical Reactions Involved 1. Formation of Iodine upon the reaction of NaIand Potassium Iodate:
Half reactions:
Reduction: 2IO3- + 12H+ + 10e- → I2 + 6H2O
Oxidation: (2I- → I2 + 2e- )
2IO3- + 12H + 10e → I2 + 6H2O
+ -

(2IO3- + 12H+ + 10I- → 6I2 + 6H2O)/2


IO3- + 6H+ + 5I- → 3I2 + 3H2O
Net Ionic Balanced Eq.: 5NaI + KIO3 + 6HCl → 3I2 + 5NaCl + KCl + 3H2O

2. Reaction of KIO3 with I2 to form the interhalogen Iodine Chloride:


Half Reactions:
Reduction: IO3- + 6H+ + 4e- → I+ + 3H2O
Oxidation: (I2 → 2I+ + 2e-)2
IO3 + 2I2 + 6H+ → 5I+ + 3H2O
-

Net Ionic Balanced Eq.: KIO3 + 2I2 + 6HCl → KCl + 5ICl + 2H2O

3. Complete balanced chemical reaction of the assay:


(5NaI + KIO3 + 6HCl → 3I2↑ + 5NaCl + KCl + 3H2O)2
(KIO3 + 2I2 + 6HCl → KCl + 5ICl + 3H2O)3
(5NaI + KIO3 + 6HCl → 3I2↑ + 5NaCl + KCl + 3H2O)2
(10NaI + 5KIO3 + 30 HCl → 10NaCl + 5KCl + 15ICl + 15H2O)/5
2NaI + KIO3 + 6HCl → 2NaCl + KCl + 3ICl + 3H2O
Factor used in the Assay f = 2 since 2 e- are lost per iodide ion.
Formula in Computing the P% and LC%
RFIS 1. Weigh about 500 mg of Sodium Iodidein a weighing bottle because it is
deliquescent
2. An iodine flask must be used in order to prevent the liberation of the iodine
gas during the titration.
3. Add 1 mL of amaranth TS. The use of amaranth TS as an indicator is
because it is not affected by highly acidic solutions.
 Amaranth is added near the endpoint since the temporary excess in the
titrant which usually occurs in the area of addition will gradually decolorize
the indicator before the endpoint is reached. The decolorization of the
indicator is irreversible.
 The volume of amaranth TS added must be small to prevent any
significant indicator error.
ASSAY OF SODIUM METABISULFITE
Analyte Sodium Metabisulfite
Official Requirement Sodium Metabisulfite contains an amount of Na2S2O5 equivalent to not less than 65.0
percent and not more than 67.4 percent of SO2
Volumetric Solution/s Used Excess Titrant: 0.1 N Iodine VS
Back Titrant: 0.1 N Sodium Thiosulfate VS
Type of Assay Iodometry
Type of Titration Residual Titration
Indicator Used Starch TS
Color Transition at Endpoint Yellow to Dark Blue
Chemical Reaction/s Involved
Factor Used in the Assay
Formula in Computing the %P or %LC
Reasons for Important Steps 1. Transfer about 200 mg of Sodium Metabisulfite to a glass-stoppered
conical flask. To prevent volatilization of iodine.
2. … containing 50.0 mL of 0.1 N Iodine VS.
3. Allow to stand for 5 minutes, protected from light. In the presence of light,
iodine undergoes a photo decomposition reaction causing it to disintegrate.
4. … add 1 mL of Hydrochloric Acid.
5. … and titrate the excess iodine with 0.1 N Sodium Thiosulfate VS.
6. … adding 3 mL of Starch TS as the endpoint is approached. Starch TS
combines with iodine to produce starch iodine complex which is indicated by
deep blue color.
ASSAY OF SODIUM NITRITE INJECTION
Analyte Sodium Nitrite
Official Requirement Sodium nitrite injection is a sterile solution of sodium nitrite in water for injections. It
contains not less than 95% and not more than 105% of the labeled amount of NaNO2.
Volumetric Solution/s Used Back titrant: 0.1N KMnO4 VS
Excess titrant: 0.1N KMnO4 VS
Excess titrant: 0.1N Oxalic acid VS
Type of Assay Permanganometry
Type of Titration Double Residual
Indicator Used
Color Transition at Endpoint Colorless – pale pink
Chemical Reactions Involved 1. Redox reaction between potassium permanganate and sodium nitrite
Half reactions:
Reduction: MnO4- + 8H+ + 5e- →Mn2+ + 4H2O
(C2O4)2- → 2CO2 + 2e-
Oxidation: H20+ NaNO2 → NO3 + 2H+
5NaNO2 + 2KMnO4 + 3H2SO4→5NaNO3 + 2MnSO4 + K2SO4 + 3H2O
Factor used in the Assay f=5
Formula in Computing the P% and LC%
RFIS 1. Adding of analyte beneath the surface of acidic mixture because this
would oxidize to nitric acid. However, if sodium nitrite were acidified with
H2SO4, which is volatile, would be lost.
2. Stand the mixture for 5 minutes to ensure completion of reaction.
ASSAY OF SODIUM THIOSULFATE INJECTION
Analyte Sodium Thiosulfate Injection
Official Requirement Sodium Thiosulfate Injection is an aqueous solution for injection. It contains NLT 95%
and NMT 105% of the labeled amount of sodium thiosulfate.
Volumetric Solution/s Used 0.1 N Iodine
Type of Assay Iodimetry
Type of Titration Direct Titration
Indicator Used Starch TS
Color Transition at Endpoint Dark blue- blue-green
Chemical Reactions Involved

Factor used in the Assay f = 2 , because thiosulfate ions must lose 2 electrons in forming one tetrathionate ion, or
each thiosulfate ion loses 1 electron
Formula in Computing the P% and LC%
RFIS 1. Adjust by the addition of 3N Hydrochloric Acid to a pH of between 6.2
and 6.7: Sodium thiosulfate is unstable in the presence of acids to prevent low
ph and low ph iodides can be oxidized to iodine by air oxygen.
2. Titrate with 0.1N Iodine VS: The concentration of the oxidizing agent may be
determined by the amount of iodine.
3. Add 3 mL of Starch TS as endpoint is approached: The iodine was
completely reduced to the iodide ion when the blue - black color
disappears.
ASSAY OF SULFUR DIOXIDE
Analyte Sulfur dioxide
Official Requirement Sulfur Dioxide contains not less than 97.0 percent, by volume, of SO2.
Volumetric Solution/s Used 0.1 N iodine VS
Type of Assay Iodimetry
Type of Titration Indirect
Indicator Used Starch TS
Color Transition at Endpoint Colorless to Pale Blue
Chemical Reactions Involved 1. Redox reaction between sulfur dioxide and iodine
Half Reactions:
Reduction: I- → I2 + 2e-
Oxidation: SO2 + 2H2O → SO42- + 4H+ + 2e
I2 + SO2 + 2H2O → 2I- + SO42- + 4H+
Factor used in the Assay f=2
Formula in Computing the P% and LC% 64.066 𝑔/𝑚𝑜𝑙
0.1 𝑁 𝑥 𝑁𝐹𝑖𝑜𝑑𝑖𝑛𝑒 𝑥 𝑉𝑖𝑜𝑑𝑖𝑛𝑒 𝑉𝑆 𝑥 1,000 𝑥
%𝑃 = 𝑥 100
𝑤𝑡 𝑠𝑎𝑚𝑝𝑙𝑒
RFIS 1. Collect 100.0 mL of gaseous sulfur dioxide over mercury, and note the
temperature of the sample and the pressure upon it.
2. Slowly introduce 50.0 mL of 0.1 N Sodium Hydroxide into the air space
over the mercury and absorb the sample in the solution by shaking.
3. … add 3 mL of starch TS.
4. … and titrate with 0.1 N Iodine VS.
ASSAY OF THYMOL
Analyte thymol
Official Requirement Thymol contains not less than 99.0 percent and not more than 101.0 percent of
C10H14O.
Volumetric Solution/s Used 0.1 N bromine VS
Type of Assay Miscellaneous
Type of Titration Direct
Indicator Used Methyl orange TS
Color Transition at Endpoint Red to colorless
Chemical Reactions Involved 1. Redox reaction involving bromide, bromate, and hydrogen ions
5KBr + KBrO3 + 6HCl → 3Br2 + 3H2O + 6KCl
Half Reactions:

5Br– + BrO3 – + 6H+ → 3Br2 + 3H2O

2. Reaction of Bromine with Thymol

Factor used in the Assay f = 4 because 1 mole of thymol reacts with 2 moles of bromine (4 equivalents)
𝑔
Formula in Computing the P% and LC% 0.1 𝑁 𝑥 𝑉𝑜𝑙𝑢𝑚𝑒 𝑜𝑓 𝑏𝑟𝑜𝑚𝑖𝑛𝑒 𝑉𝑆 𝑥
150.22
𝑚𝑜𝑙
1,000 𝑥 4
%𝑃 = 𝑥 100
𝑤𝑡 𝑠𝑎𝑚𝑝𝑙𝑒

RFIS 1. Transfer about 100 mg of Thymol to a 250-mL iodine flask. The flask must be
stoppered at all times after the addition of reagents to prevent the loss of
bromine.
2. Dissolve in 25 mL of 1 N Sodium Hydroxide. Thymol is only slightly soluble in
water at neutral pH, but it is extremely soluble in alcohols and other organic
solvents, as well as in strongly alkaline aqueous solutions due to deprotonation
of the phenol (Raju, 2017). NaOH is a strong base and will pull the H from the -
OH on the thymol ring, leaving the -O (with a negative charge) much more
water soluble (Jansen, 2012).
3. Add 20 mL of hot dilute hydrochloric acid (1 in 2). Serves as the source of
H+ ions that oxidize bromide and reduce bromate, both to form bromine.
(Denby, 2006).
4. Warm the solution to between 70O and 80O. Bromine or iodine can be formed
when heating bromides or iodides in the presence of oxidizing agents (Svehla,
1996, p. 4).
5. … add 2 drops of Methyl Orange TS. Molecular bromine produced in the first
part of the assay reacts instantly with the phenol to form 2,4,6-tribromophenol
As soon as sufficient bromine has been poduced to react with the fixed amount
of phenol, free bromine will appear in the solution. This bromine will
immediately bleach the methyl orange solution.
6. … and continue the titration slowly, swirling vigorously after each addition.
The swirling of the solution is important to ensure that the titrant is evenly
combined with analyte and also to avoid the formation of 2 separate layers that
wouldn’t react with each other causing erroneous titration (Scalabrin, 2019)
ASSAY OF TITANIUM DIOXIDE
Analyte Titanium dioxide
Official Requirement Titanium Dioxide contains not less than 99.0 percent and not more than 100.5
percent of TiO2, calculated on the dried basis. If labeled as attenuation grade, then
Titanium Dioxide contains not less than 99.0 percent and not more than 100.5 percent of
TiO2, calculated on the ignited basis. Attenuation grade material may con-tain suitable
coatings, stabilizers, and treatments to assist formulation.

NOTE—If labeled as attenuation grade, then all tests and assays are conducted on
uncoated, un-treated material. For UV attenuation grade, the test for Loss on drying does
not apply. The FDA requires the content of lead to be not more than 10 ppm, that of
antimony to be not more than 2 ppm, and that of mercury to be not more than 1 ppm
Volumetric Solution/s Used 0.1 N potassium permanganate
Type of Assay Permanganometry
Type of Titration Indirect with blank
Indicator Used Self-indicating
Color Transition at Endpoint Colorless to Faint Pink that persists for 5 minutes
Chemical Reactions Involved 1. Reaction of titanium dioxide with sulfuric acid
TiO2 + 2H2SO4 → Ti(SO4)2 + 2H2O

2. Reaction with Jones reductor


Ti4+ + zinc amalgam → Ti3+

3. Redox reaction between potassium permanganate and reduced titanium (IV)


Reduction: MnO42- + 8H+ + 5e- → Mn2+ + 4H2O
Oxidation: Ti3+ + H2O → TiO2+ + 2H+ + 2e-
Factor used in the Assay
Formula in Computing the P% and LC% 𝑉 𝑥 𝑚𝑒𝑞 𝑤𝑡 𝑤𝑡 𝑥 100
%𝐿𝐶 =
𝑤𝑡 𝑠𝑎𝑚𝑝𝑙𝑒
RFIS 1. ... add 20 mL of sulfuric acid. Titanium dioxide is soluble in hot sulfuric acid.
2. and 7 to 8 g of ammonium sulfate. Addition of ammonium sulfate promotes
dissolution of titanium dioxide in sulfuric acid.
3. Mix, heat on a hot plate until fumes of sulfur trioxide appear, and
continue heating over a strong flame until solution is complete or it is
apparent that the undissolved residue is siliceous matter. Cool,
cautiously dilute with 100 mL of water, stir, heat carefully to boiling while
stirring, and allow the insoluble matter to settle.
4. Filter, transfer the entire residue to the filter, and wash thoroughly with
cold 2N sulfuric acid.
5. Dilute the filtrate with water to 200 mL, and cautiously add about 10 mL of
ammonium hydroxide. Addition of ammonium hydrixide is done to neutralize
filtrate.
6. Prepare a zinc amalgam column. Zinc amalgam inhibits the reduction of
hydrogen ions by zinc.
7. Wash the zinc amalgam column with 100-mL portions of 2N sulfuric acid
until 100 mL of the washing does not decolorize 1 drop of 0.1 N
potassium permanganate. This is done to remove any organic matter that
may be present in the solution.
8. Place 50 mL of ferric ammonium sulfate TS in a 1000-mL suction flask.
Ferric ammonium sulfate stabilizes the reduced solution in the filter flask.
9. ... add 0.1 N potassium permanganate until a faint pink color persists for
5 minutes. This implies that there are no reducing substance left in the
column.
10. ... pass 50 mL of 2N sulfuric acid through the reductor at a rate of about
30 mL per minute. This is done in order to wash out all of the reduced
compound and also the acid, which would cause unnecessary consumption of
the zinc.
11. Pass the prepared titanium solution through the reductor at the same rate, and
follow with 100 mL each of 2N sulfuric acid and of water.
12. ... keep the reductor filled with solution or water above the upper level of
the amalgam. The solution containing an equivalent amount of Ti3+ must be
collected in an inert atmosphere becaus of the relative ease with which Ti3+ is
oxidized in air.
13. ....and titrate immediately with 0.1 N potassium permanganate VS.
Immediate use of the reductor is done to prevent formation of basic salts.
14. Perform a blank determination, substituting 200 mL of 2N sulfuric acid for
the assay solution, and make any necessary correction..