MOISTURE DETERMINATION

 Official Drugs vary in their water content.

 Water available either as water of crystallization (hydrates) or as water in the adsorbed form.
 Determination of this constant is necessary to specify certain water content limits in the drug
monographs.

Water Content is determined by any one of the SIX METHODS

1. Gravimetric Method – for drugs containing no constituents other than water, volatile at 105C.
2. Gravimetric Method – for drugs containing ether-soluble constituents, volatile at 105C.
3. Azeotropic Method or toluene distillation - for the determination of moisture content of many
vegetable drugs containing 2% or more of moisture
4. Titrimetric Method or Karl Fischer Method - for crystalline compounds that contain water of hydration
or absorbed water
5. Dew Point Method – for determining Water at Very Low Concentration
6. Electrolytic Hygrometric – for determining Extremely Low Concentration of Water

WATER CONTENT DETERMINATION OFFICIAL METHODS

METHOD I. Titrimetric Method/ Karl-Fischer Method

Ia – direct Titration
Ib – Residual titration
Ic - Coulomteric titration
“1 mL of the reagent is equivalent to approximately 5 milligrams of water”

• This method is the most rapid, requires only a small sample and is specific for water.
• The method involves titration of the sample in reagent methanol with Karl Fischer reagent, which
consists of iodine, sulfur dioxide, pyridine, and methanol.
• The Karl Fischer reagent has a concentration such that one mL of the reagent is equivalent to
approximately five milligrams of water. (1 ml = 5 mg of water)
• The reagent deteriorates gradually; it is standardized by employing sodium tartrate (Na2C4H4O6.2H2O)
as a primary standard.

• The water equivalence (F) mg of water per mL of the reagent is given by the formula

0.1566 X W
V
• Where W is the weight in mg of sodium tartrate and V is the volume in mL of the reagent required.

• Percent Water Content is given by the formula

BR x F
%Water Content = x 100
Wt
• Where BR (Volume of Reagent used), F (Water Equivalence) and Wt (Weight of sample)
 Practice Problem

1. Moisture content of citric acid was determined by the Karl-fischer Method and the following data were
obtained
wt of citric acid …………………………4.8 g
vol of reagent used ……………………20 ml
Water equivalence factor of the reagent was determined by titrating 0.350 g of sodium tartrate with 10 ml
of KFR, determine the water content of citric acid
0.1566 x W
F=
V
0.1566 x 350 mg
F=
10 mL
F=5.841

BR x F
%Water Content= x 10 0
Wt
20 mL x 5.841
%Water Content= x 10 0
4800 mg
% Water Content = 2.43%

METHOD II. Azeotropic Method/ Distillation Method

• The Azeotropic Method is specified for the determination of moisture content of many vegetable drugs
containing 2% or more of moisture.
• Its disadvantage is the need for a large amount of drug, from fifty (50) to one hundred (100) grams
must be used in order to secure a volume of water that can be measured conveniently without
considerable error.

METHOD III. Gravimetric Method/ Drying/Thermal Method

Method of choice for chemical samples (1-2 grams), vegetable drugs and biologics
• When the drug contains matter other than water which is volatile at 105C, the volatile ether soluble
extractive must be determined and the weight of this extractive is subtracted from the weight less by
the drug upon drying, the difference is the moisture content of the drug.

Online Assessment: (Email your assessment at jdbarlis@fatima.edu.ph, for questions/inquiries please free to
message in this Group chat)

1. From the assay of sodium citrate sample using Karl Fischer method, the following results were obtained:
Wt of sample 3.65 g sample
Vol of titrant 20 ml
Wt of primary standard 235 mg
Vol consumed during titration 7.46 ml
a. Determine the water equivalence factor
b. Compute for % water