Primary and Secondary Standard – Pharmaceutical Analysis 1 B. Pharma 1st semester

Primary and Secondary Standard

Primary and Secondary Standard - Pharmaceutical Analysis 1 B. Pharma 1st semester

Learning Objectives

At the end of this lecture, the student will be able to

• Explain about different types of substances used in volumetric analysis

• Explain about the primary and secondary standard substances

• Explain how to prepare and store primary standard substances: Sodium oxalate, ceric ammonium sulphate

• Explain the secondary standard substances

• Explain how to prepare and store secondary standard substances: Sodium hydroxide, Potassium Hydrogen Phthalate, Hydrochloric acid, Sodium thio sulphate and Potassium permanganate

Primary and Secondary Standard

1. Primary standard substances-

The reagent is ready to be weighed and used to prepare a solution with a known concentration (standard)

Properties of primary standard substances:

(a) It is extremely pure

(b) Highly stable

(c) It is anhydrous

(d) It is less hygroscopic

(e) Has very high molecular weight

(f) Can be weighed easily

(g) Should be ready to use and available

(h) Should be preferably non toxic

(i) Should not be expensive

2. Secondary standard:

A secondary standard is a standard that is prepared in the laboratory for a specific analysis. It is usually standardized against a primary standard

Standardization:
The process by which the concentration of a secondary standard substance is determined by titration with a known concentration of a primary standard substance

Examples of Primary Standard Substances

• Benzoic acid for standardization of waterless basic solutions: Ethanolic sodium and potassium hydroxide, TBAH, and alkali methanolates in methanol, isopropanol, or DMF

• Potassium bromate (KBrO3), Potassium dichromate (K2Cr2O7) for standardization of sodium thiosulfate solutions

• Potassium hydrogen phthalate (usually called KHP) for standardization of perchloric acid in acetic acid solutions and aqueous base like sodium hydroxide

• Arsenic trioxide for making sodium arsenite solution for standardization of sodium periodate solution

• Sodium carbonate (anhydrous) for standardization of aqueous acids: hydrochloric, sulfuric acid and nitric acid solutions (but not acetic acid)

• Sodium chloride (anhydrous) for standardization of silver nitrate solutions

• Sulfanilic acid for standardization of sodium nitrite solutions

• Zinc powder, after being dissolved in sulfuric or hydrochloric acid, for standardization of EDTA solution

Examples of Secondary Standard Substances

Acid-base titrations:

Acid: Hydrochloric acid, sulphuric acid, oxalic acid

Base:  sodium hydroxide, potassium hydroxide

Redox titration:

Oxidising agents: Potassium permanganate, Iodine

Reducing agents: Sodium thio sulphate, potassium iodide

Precipitation titration: Silver nitrate, ammonium thiocyanate

Complexometric titration: EDTA

Preparation and Storage of Primary Standard Substances: Sodium Oxalate

Preparation and storage of: Sodium Oxalate: C2Na2O4

Mol weight = 133.99

Eq.wt:67

Chemicals required to prepare sodium oxalate: Sodium Oxalate and Distilled Water

Preparation: Preparation of 0.1 N Solution

•Dry sodium oxalate (C2Na2O4) at 100oC to constant mass for at least two hours and cool

•Dissolve 6.700g of dried material in water and dilute to 1000 ml

 Storage:

•Store in a tightly closed container

•Store in a cool, well-ventilated area away from incompatible substances

•Oxalates slowly corrode steel

Example sum:

1. How do you prepare 0.1N concentration of sodium oxalate solution of 100 ml volume?

Calculation:

                            Weight of the substancex1000

Normality=————————————————-

                     Equivalent weight x volume required

2.  Sodium oxalate of 8.5 g has been weighed for the experiment and dissolved in 500 ml of distilled water.

Calculate the Molarity of the given solution.

Preparation and Storage of Primary Standard Substances: Ceric Ammonium Sulphate

Preparation and storage of: Ceric Ammonium Sulphate: 0.1 M  (Ce(SO4)2. 2(NH4)2SO4.4H2O

Mol wt: 668.58

Chemicals required to prepare ceric ammonium sulphate: Ceric Ammonium Sulphate, H2SO4 and Distilled Water

Preparation:

• Dissolve 67g of ceric ammonium sulphate, with the aid of gentle heat, in a mixture of 30 ml of sulphuric acid

•Add 500 ml of water cool, filter the solution, if turbid

•And dilute to 1000 ml with water

Ceric ammonium sulphate has 4 moles of water of crystallization so it is secondary in nature and it is standardised by arsenic trioxide as per IP

Ceric Ammonium Sulphate, 0.1 M

Standardise the solution in the following manner: Procedure

• Weigh accurately about 0.2 g of arsenic trioxide, previously dried at 105 º for 1 hour

• Transfered to a 500-ml conical flask

• Wash down the inner walls of the flask with 25 ml of an 8.0 per cent w/v solution of sodium hydroxide

• swirl to dissolve, add 100 ml of water and mix

• Add 30 ml of dilute sulphuric acid

• 0.15 ml of osmic acid solution

• 0.1 ml of ferrroin sulphate solution and

• Slowly titrate with the ceric ammonium sulphate solution

• Until the pink colour is changed to a very pale blue
adding the titrant slowly towards the end-point

1 ml of 0.1 M ceric ammonium sulphate is equivalent to 0.004946 g of As2O3

Ceric Ammonium Sulphate: Principle involved in standardisation:

• Ceric being an oxidising agent is titrated against arsenic trioxide, a reducing agent in the presence of osmic acid as a catalyst and sulphuric acid.

• Simultaneous oxidation and reduction take place, where ceric gets reduced to cerrous ions and arsenic trioxide gets oxidised to arsenious acid

• In the presence of Ferroin as an indicator, the endpoint is red to blue

Preparation and Standardisation of Secondary Standard Substances: Sodium Hydroxide

Introduction:

• Sodium hydroxide (NaOH), also known as lye and caustic soda is an inorganic compound

• White solid and highly caustic metallic base and alkali salt

• Available in pellets, flakes, granules

•Prepared solutions: number of different concentrations

•Sodium hydroxide forms an approximately 50% (by weight) saturated solution with water

•Sodium hydroxide is soluble in water, ethanol and methanol

•Deliquescent and readily absorb moisture and carbon dioxide in air

Why sodium hydroxide is considered as secondary standard substances?

Alkaline solutions absorb carbon dioxide from the atmosphere according to the reaction:

CO2 +   2OH – ßà CO3 2- + H2O

Since hydroxide ion is consumed by this reaction, the concentration of a standard sodium hydroxide solution will be changed

2 NaOH (s) + CO2 (g) →Na2CO3 (aq) + H2O (l)

Preparation of Sodium Hydroxide

Sodium hydroxide: NaOH

Mol Weight= 40

Equivalent weight: 40

To prepare 0.1N concentration:

Equation to calculate normality or molarity of a solution

                                                           Weight of the substancex1000 
Normality/Molarity= ————————————————————-

                                       Equivalent weight/ Mol weight x volume required

Chemicals required to prepare 0.1N sodium hydroxide solution

Sodium hydroxide and Distilled Water

Preparation and Storage of: Sodium Hydroxide: 0.1N

1. Weigh about 0.4 gm of A.R. Sodium hydroxide into a 100 ml volumetric flask

2. Dissolve in small volume of distilled water

3. Make up the mark with distilled water

Storage: Store in a air tight container In a cool dry place

Standardisation of Sodium Hydroxide

• To determine the concentration of a sodium hydroxide solution through a titration

•The primary standard must be an acid

•In the present experiment, potassium hydrogen phthalate (KHP =KC8H5O4) will be used

NaOH(aq) + KHC8H4O4(aq) → KNaC8H4O4(aq) + H2O(l)

Preparation and Standardisation of Secondary Standard Substances: Potassium Hydrogen Phthalate

Introduction:

• Potassium hydrogen phthalate, often called simply KHP, is an acidic salt compound

• It forms white powder, colorless crystals, a colorless solution, and an ionic solid that is the monopotassium salt of phthalic acid

• KHP is slightly acidic, and

•Used as a primary standard for acid-base titrations because it is solid and air-stable, making it easy to weigh accurately

•It is not hygroscopic

•Used as a primary standard for calibrating pH meters because, its pH in solution is very stable

Preparation and storage of:

Potassium hydrogen phthalate: KHC8H4O4

Mol Weight= 204.22 g/mol

Equivalent weight: 204.22

To prepare 0.1N concentration:

Note: Dry primary standard potassium hydrogen phthalate at 110°C for two hours before weighing

Chemicals required to prepare 0.1N potassium hydrogen phthalate solution

Potassium hydrogen phthalate and Distilled Water

Preparation of Potassium Hydrogen Phthalate

Step: 1. Weigh the required quantity of PHT             

Step: 2.Transfer PHT into a 100 ml volumetric flask

Step: 3.Make up the mark with distilled water

Standarisation of 0.1N Sodium Hydroxide Using Potassium Hydrogen Phthalate

Step: 1. Fill the burette with 0.1N potassium hydrogen phthalate

Step: 2. Pipette out 10 ml of prepared 0.1N solution of sodium hydroxide into conical flask

Step: 3. Add 2 drops of Phenolphthalein as indicator

Step: 4. Titrate the sodium hydroxide solution against PHT until pink changes to colorless

Step: 5.Repeat the titration until consecutive concordant readings are obtained

Step: 6. Calculation:

Formula: N1V1=N2V2

Where,

N1  = Normality of Primary standard substance

V1  = Volume of primary standard substance taken for titration

N2   = Normality of secondary standard substance (Changed one)

V2    = Volume of secondary standard substance consumed

N1V1     N2V2

——– = ——–

n1           n2

Step: 7. Report: The exact normality of the secondary standard substance was found to be:——— N

Preparation and Standardisation of Secondary Standard Substances: Hydrochloric Acid

Introduction:

• Hydrochloric acid is a clear, colorless, highly pungent solution of hydrogen chloride gas in water

• It was historically called acidum salis, muriatic acid, and spirits of salt

• It is a highly corrosive, strong mineral acid with many industrial uses

• Hydrochloric acid is found naturally in gastric acid

• Chemically it is a strong acid

Why hydrochloric acid is considered as secondary standard substances?

• Hydrochloric acid, HCl, and sulfuric acid, H2SO4, are NOT suitable for use as a primary standard because although they are both commercially available as concentrated solutions that are easily diluted, the concentration of the “concentrated” solution is NOT accurately known

• Laboratory grade hydrochloric acid is not sufficiently pure

Preparation of Hydrochloric Acid

Hydrochloric acid: HCL Mol Weight= 36.5

Equivalent weight: 36.5

Note: Since hydrochloric acid is liquid the mass after calculation should be concerted to volume using the formula:

Preparation of Hydrochloric Acid

Chemicals required to prepare 0.1N hydrochloric acid solution

Hydrochloric acid and Distilled Water

Preparation and Storage of Hydrochloric Acid: 0.1N

1. Pipette out 9 ml of hydrochloric acid into a 100 ml volumetric flask

2. Dissolve in small volume of distilled water

3. Make up the mark with distilled water

Storage: Store in a air tight container In a cool dry place

Standardization of Hydrochloric Acid

• Sodium carbonate (also known as washing soda, soda ash and soda crystals), Na2CO3, is the sodium salt of carbonic acid (soluble in water)

• Crystalline heptahydrate, which readily effloresces to form a white powder, the monohydrate

• Pure sodium carbonate is a white, odorless powder that is hygroscopic (absorbs moisture from the air)

• Has an alkaline taste

• Forms a strongly alkaline water solution

• Sodium carbonate is well known domestically for its everyday use as a water softener

• To determine the concentration of a hydrochloric acid solution through a titration

• The primary standard must be an base

• In the present experiment, anhydrous sodium   carbonate will be used

Na2CO3 +2HCl ßà  2NaCl + H2O + CO2

1 mole 2 moles           2 moles 1 mole 1 mole

Preparation and Standardisation of Secondary Standard Substances: Anhydrous Sodium Carbonate

Anhydrous sodium carbonate: Na2CO3

Mol Weight= 105.99

Chemicals required to prepare 0.1N anhydrous sodium carbonate solution

Anhydrous sodium carbonate

Preparation of Anhydrous Sodium Carbonate

Step 1. Weight out approximately 2 grams of solid sodium carbonate on a clean, dry watch glass

Step 2.Place watch glass in an oven at a temperature above 100oC (to ensure all the water is evaporated out) but less than 270oC (to ensure the carbonate does not decompose). A temperature of approximately 260oC is often used

Step 3. After 30 minutes, remove the watch glass from the oven and transfer it immediately to a desiccator to prevent the sodium carbonate from re-absorbing water from the atmosphere

Step 4.Allow the sodium carbonate to cool in the desiccator before re-weighing it

Step 5. Repeat this heating-cooling-weighing process until a constant weight is achieved (indicating that all the water has been driven off)

Preparation of Anhydrous Sodium Carbonate

Step: 1. Weigh the required quantity of anhydrous sodium carbonate

Step: 2.Transfer into a 100 ml volumetric flask

Step: 3.Make up the mark with distilled water

Standarisation of 0.1N Hydrochloric Acid Using Anhydrous Sodium Carbonate

Step: 1. Fill the burette with 0.1N Anhydrous Sodium Carbonate

Step: 2. Pipette out 10 ml of prepared 0.1N solution of hydrochloric acid into conical flask

Step: 3. Add 2 drops of methyl orange as indicator

Step: 4. Titrate the hydrochloric acid solution against anhydrous sodium carbonate until red to yellow

Step: 5.Repeat the titration until consecutive concordant readings are obtained

Step: 6. Calculation:

Formula: N1V1=N2V2

Where,

N1 = Normality of Primary standard substance

V1  = Volume of primary standard substance taken for titration

N2  = Normality of secondary standard substance (Changed one)

V2   = Volume of secondary standard substance consumed

N1V1/n1              =             N2V2/n2

Step: 7. Report: The exact normality of the secondary standard substance was found to be:——— N

Preparation and Standardisation of Secondary Standard Substances: Sodium Thio Sulphate

Why sodium thiosulphate is considered as secondary standard substances?

• Sodium thiosulphate contains water of crystallisation, so it efflorescent in nature

Preparation and storage of: Sodium thio sulphate: Na2S2O3 .5H2O

Mol Weight= 248.184

Chemicals required to prepare 0.1N sodium thio sulphate solution: sodium thio sulphate, anhydrous sodium carbonate

Preparation and Storage of Sodium Thio Sulphate: 0.1N

1. Weigh the required quantity of sodium thio sulphate into a 100 ml volumetric flask

2. Dissolve in small volume of distilled water free from carbon di oxide

3. Add 0.2 g of sodium carbonate

4. Make up the mark with distilled water

Storage: Store in a air tight container in a cool dry place

The stability of thio sulphate solution:

1. The ordinary distilled water contains excess of carbon di oxide, this may cause a slow decomposition to take place with the formation of sulphur

S2O3 2- + H+ = HSO3 + S

2. Decomposition can also be caused by bacterial action: Thiobacilluc thioparus

Standardisation of 0.1 Sodium Thio Sulphate

• Standarisation of sodium thio sulphate: Can be standarised with the titration of the iodine when unmeasured excess of potassium iodide is added to known volume of an acidified standard potassium dichromate solution:

6KI+14HCl+ K2Cr2O7 → 2CrCl3+3I2  +7H2O+8KCl

2Na2S2O3  + I2 → Na2S4O6  + 2NaI

•Each mole of dichromate  results in the production of three moles of iodine meqK2Cr2O7 = M/6

Preparation of Potassium dichromate solution: 0.1N

Chemicals required to prepare 0.1N Potassium dichromate solution

Potassium dichromate, Potassium iodide, Hydrochloric acid and Starch

Preparation and Storage of Potassium Dichromate: 0.1N

1. Weigh about 0.49 g of potassium dichromate into a 100 ml volumetric flask

2. Dissolve in small volume of distilled water

3. Make up the mark with distilled water

Storage: Store in a air tight container in a cool dry place

Standardisation of Sodium Thio Sulphate

1. Load a burette with standardised sodium thiosulphate solution

2. Pipette 10-ml aliquot of prepared standard potassium dichromate solution into 100 ml flask

3. Add 10 ml of 10 % KI solution and 10 ml of 1 M HClsolution

4. Cover the flask with a stopper and put into dark place at 10 min

5. Titrate the sample solution with thiosulfate until the solution becomes pale yellow

6. Introduce 5 drops of starch indicator, and titrate with constant stirring to the disappearance of the blue colour

7. Read the burette mark

8. Calculate precision normality (molarity) of the sodium thiosulphate standard solution

Preparation and Standardisation of Secondary Standard Substances: Potassium Permanganate

Introduction:

• Potassium permanganate is a dark purple or brownish black powder or dark purple or almost black crystals

• It is soluble in cold water and freely soluble in boiling water

• It is a strong oxidising agent

• It decomposes on contact with certain organic substances

The permanganate ion is strong oxidizing reagent. The half-reaction is:

MnO4- + 8H+ + 5e- ßà Mn2+ + 4H2O                   

E0 = 1.51 V

Why potassium permanganate is considered as secondary standard substances?

• Because it contains reduced products like manganese oxide MnO2

• The concentration of KMnO4 changed after preparation because it dissociated through reducing agents such as ammonia and organic substances in water

• keep it at least 7-10 days after preparation at dark place and in a dark bottle

Preparation of Potassium Permanganate

Potassium permanganate: KMNO4

Mol Weight=158.03

Preparation and Storage of Potassium Permanganate: 0.1N

• Dissolve about 0.32 g of KMnO4 in 100 mL of deionized water using a large beaker

• Cover that beaker with a watch-glass and heat to boiling using a hot plate in the hood

• Keep the solution at a gentle boil for about 1 hr

• Let the solution stand overnight

• Remove Manganese di oxide by filtering through a filter crucible

• Transfer the solution to a clean amber glass- stoppered bottle

• Store in the dark when not in use

Precaution during preparation of potassium permanganate solution:

• Before filtration, the reagent solution is allowed to stand for about 24 hrs or

• Heated for a brief period to hasten oxidation of the organic species generally present in small amounts in distilled and deionised water

• Paper cannot be used for filtering because permanganate ions react with it to form additional manganese dioxide

Chemicals required to prepare 0.1N Potassium permanganate

Potassium permanganate

Amber bottle for storage

Standarisation of Potassium Permanganate

• To determine the concentration of a potassium permanganate solution through a titration: The primary standard must be a reducing agent

• In the present experiment, Sodium oxalate is used as primary standard substance, as reducing agent

• The titration follows oxidation-reduction reaction in an acidic media

5C2O 2- + 2MnO41- + 16 H+ →2Mn2+ +8H2O+10CO2

Over all Equation:

Na2C2O4 + H2SO4 = H2C2O4 + Na2SO4

2KMnO4 + 5H2C2O4 + 3H2SO4 = K2SO4 + 2MnSO4 + 10CO2 + 8H2O

Preparation of Sodium Oxalate

Introduction:

Sodium oxalate, Na2C2O4, is a strong electrolyte that dissociates completely in water according to the following equation:

Na2C2O4 à2 Na+ (aq) +  C2O4 (aq)

Sodium oxalate: Na2C2O4

Mol Weight= 134

The half-reaction for oxalate as a reducing agent is

C2O4 2- – 2e- →2CO2

The equivalent mass of Na2C2O4 = 2(22.99) +2(12.01)+4(16.00)/2 = 67.00

To prepare 0.1N concentration :

Equation to calculate normality or molarity of a solution

                                   Weight of the substancex1000

Normality/Molarity= ———————————————————–

                                       Equivalent weight/ Mol weight x volume required

Chemicals required to prepare 0.1N sodium oxalate solution

Sodium oxalate

Preparation of Sodium Oxalate

Step: 1. Weigh the required quantity of sodium oxalate

Step: 2.Transfer PHT into a 100 ml volumetric flask and dissolve with distill water

Step: 3.Make up the mark with distilled water

Standarisation of 0.1N Potassium Permanganate Using Sodium Oxalate

Step:  1.Fill the burette with 0.1N potassium permanganate solution

Step: 2.Pipette out 10 ml of prepared 0.1N solution of sodium oxalate into conical flask

Step: 3. Add 7 ml of sulfuric acid into conical flask and heat to 70 o C

Step: 4.Titrate the sodium oxalate against potassium permanganate solution until pink is discharged

Note: Potassium permanganate acts as self-indicator

Step: 5.Repeat the titration until consecutive concordant readings are obtained

Step: 6. Calculation:

Formula: N1V1=N2V2

Where,

N1 = Normality of Primary standard substance

V1 = Volume of primary standard substance taken for titration

N2 = Normality of secondary standard substance (Changed one)

V2 = Volume of secondary standard substance consumed

N1V1  = N2V2

Step: 7. Report: The exact normality of the secondary standard substance was found to be:——— N

Precaution during standarisation of potassium permanganate solution:

Sufficient sulphuric acid is added during standarisation because potassium permanganate oxidation ability is better in acidic media and to keep ion concentration constant thorough out the standarisation process

MnO + 8 H+ + 5e→ Mn2+ + 4H2O

Effect of temperature:

• Near 70oC to be maintained throughout the titration because the oxidation of sodium oxalate is rapid enough at such temperature

• Below 60o C the reaction is very slow

• Formation of brown colour during the titration is caused by:

Insufficient acid

Applying too-high temperature

The use of a dirty flask

Summary:

Primary standard substances- The reagent which is ready to be weighed and used to prepare a solution with known concentration (standard)

Secondary standard: is a standard that is prepared in the laboratory for a specific analysis.  It is usually standardized against a primary standard

Standardization:  The concentration of a secondary standard substance is determined by titration with a known concentration of primary standard substance

• Equation to calculate normality or molarity of a solution

                                                         Weight of the substancex1000

Normality/ Molarity = ———————————————————-

                                        Equivalent weight/ Mol weight x volume required

• Sodium hydroxide is considered to be secondary standard substance as it absorbs moisture from the atmosphere can be standardised by potassium hydrogen phthalate

• Hydrochloric acid concentration various as it is a fuming liquid can be standardised by anhydrous sodium carbonate

• Sodium thio sulphate is considered as secondary standard as it is efflorescent in nature: as it contains 5 moles water of crystallization

• Sodium thio sulphate is standarised by using potassium di chromate

• Potassium permanganate is considered to be secondary standard substance as it gets decomposed by organic matter to manganese di oxide

• Potassium permanganate can be standarised by using sodium oxalate in presence of acidic media and at a temperature of 60 -70 o C

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