Page 42 - Pharmaceutical Analytical Chemistry II - Pharm D Clinical- 07-PA202

Karl Fischer reagent for determination of moisture content

Reagent
Iodine, sulfur dioxde dissolved in pyridine (I2, SO2 exist as complex to

prevent their volatilization) and xss methanol

C5H5N C5H5N.I2 C5H5N.SO2 MeOH

Application

Determination of water in organic liquids and solids which are soluble

in methanol and can be analyzed by direct titn (acids, alcohols, esters,
anhydrides…)

Reaction
Redox reaction

I2 + SO2 + (H2O) 2HI + SO3

C5H5N.I2 + C5H5N.SO2 + C5H5N + H2O 2C5H5N.HI + C5H5N.SO3

Role of MeOH

Pyridine / SO3 complex is capable of consuming water;

C5H5N.SO3 + H2O C5H5NHSO4H
Pyridinium hydrogen sulfate

This reaction is undesirable and can be prevented by xss MeOH
(more reactive than water)

C5H5N.SO3 + CH3OH C5H5N(H)SO4CH3
Pyridinium methyl sulfate

Method Direct titration

Ep detection
Color change from yellow (reaction products) to brown (xss reagent,
pyridine iodine cpx) OR potentiometric

Stoichiometry
1 mole of I2, 1 mole of SO2, for each mole of H2O.

I2 ≡ H2O

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