NON - AQUEOUS

 NON-AQUEOUS TITRATION

MOST COMMON TITRIMETRIC PROCEDURE

pharmaCOPOEIAL ASSAYS

 NON-AQUEOUS TITRATION used in?

 NON-AQUEOUS TITRATION

refers to a type of titration in which the analyte substance is dissolved in a solvent that DOES NOT CONTAIN WATER.

BRONSTED-LOWRY 

PRINCIPLE behind Non-aqueous Titration

donor 

BRONSTED-LOWRY 

• Acid is a proton —-

acceptor

BRONSTED-LOWRY 

• Base is a proton ——

APROTIC solvents

NEUTRAL in charge

APROTIC solvents

chemically inert

APROTIC solvents

generally have a low dielectric constant.

• chloroform 

• benzene

APROTIC solvents EXAMPLE

PROTOPHILIC solvents

BASIC character

PROTOPHILIC solvents

tend to react with the acids they come in contact with, leading to the formation of solvated protons.

• ammonia 

• pyridine.

PROTOPHILIC solvents EXAMPLE

 PROTOGENIC solvents

MORE ACIDIC character

 PROTOGENIC solvents

tend to have a levelling effect on the bases they come in contact with.

• sulphuric acid 

• acetic acid.

 PROTOGENIC solvents EXAMPLE

AMPHIPROTIC solvents

PROTOPHILIC as well as PROTOGENIC

• acetic acid 

• alcohols

AMPHIPROTIC solvents EXAMPLE

Perchloric acid in glacial acetic acid or dioxane

 TITRANTS - ACID

• Sodium methoxide

• Lithium methoxide in ethylenediamine

• N-butylamine

• morpholine

 TITRANTS - BASE

• Methyl orange

• methyl red

• Thymol blue 

INDICATORS

ACIDIMETRY

• RELATIVELY STRONGER

• Crystal violet

• Malachite green

• Quinaldine red

• Methylrosaniline

INDICATORS

ACIDIMETRY

• WEAK BASES

 potentiometric methods

INDICATORS

ALKALIMETRY

• MOST PREFERRED

Thymol blue

INDICATORS

ALKALIMETRY

• STRONG ACID

Azo violet 

INDICATORS

ALKALIMETRY

• WEAK ACIDS

KJELDAHL METHOD

Nitrogen determination

KJELDAHL METHOD

A method designed to determine and quantify AMMONIA in AMMONIUM SULFATE obtained by decomposing organic substance with sulfuric acid 

• K2SO4, anhy Na2SO4 

• CuSO4, Se 

• if N is as NO3, salicylic acid is added 

AMMONIA in AMMONIUM SULFATE

KJELDAHL METHOD

A method designed to determine and quantify ———— obtained by decomposing organic substance with sulfuric acid 

macroanalysis

USP METHODS 

Method I:  

semi-microanalysis

USP METHODS 

Method II:

• If reactants are insoluble in water such as organic acids and bases 

• If reactants are reactive with water

  Most organic acids and bases are weak acids and bases 

• Moisture must be avoided or at least limited to 0.05%

NON-AQUEOUS TITRATION

WHEN TO USE?

• Titration of water insoluble drugs 

• Titration of weakly acidic and basic drugs

• Titration of water sensitive drugs like ASA and polyphenols 

• Wider pH range as compared to water 

• Simple, fast, precise and accurate

ADVANTAGES of NON-AQUEOUS TITRATION

• temperature, moisture and co2 should be controlled properly 

• expensive solvents 

• volatile solvents 

• some are hazardous

DRAWBACKS