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Karl Fischer Titration

This document discusses methods for determining the water content of samples using volumetric Karl Fischer titration. It describes the principles, equipment, reagents, procedures for standardization and analysis, calculations, and provides an example analysis of lidocaine HCl to determine water content.

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ginga716
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498 views28 pages

Karl Fischer Titration

This document discusses methods for determining the water content of samples using volumetric Karl Fischer titration. It describes the principles, equipment, reagents, procedures for standardization and analysis, calculations, and provides an example analysis of lidocaine HCl to determine water content.

Uploaded by

ginga716
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
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Jarubol Chaichana

Bureau of Drug and Narcotic


Department of Medical Sciences
2 March 2012
1
Principle -The titrimetric determination of water is
based upon the quantitative reaction of water with
an anh solution of sulfur dioxide and iodine in the
presence of a buffer that reacts with hydrogen ions.
2
Method 1a (Direct Titration)
<921> Water Determination
USP34
Principle - The semi-micro determination of water
is based upon the qunatitative reaction of water
with sulfur dioxide and iodine in a suitable anh
medium in the presence of a base with sufficient
buffering capacity.
3
Method 1 (Ph.Eur.method 2.5.12)
Determination of Water
BP 2012
In the volumetric titration method,
iodine required for reaction with water is
previously dissolved in water determination,
and water content is determined by measuring
the amount of iodine consumed as a result of
reaction with water in a sample.
4
This is a specific method. Only water will be
determined. The method is rapid (a few
minutes).
With KF titration both free and bound water
can be determined, e.g. surface water on
crystals or the water contained
inside them.
5
e.g. Cloxacillin sodium (BP2012).(2.5.12)
Water : 3.0% to 4.5%, determined on 0.3 g
It is indicated that when determined by
accurately weighed about 0.3 g of the sample
and performing KF Titration, the water content
is NLT 3.0% and NMT 4.5% of the sample weight.
6
Volumetric KF Titration
7
Analytical balance (min resolution 0.1 mg)
Syringe with long, thin needle
Karl Fischer reagents for volumetric water determination
KF instrument should not be set up in areas that are subject
to large temp fluctuations, high humidity. They must not be
placed in the proximity of heating, cooling devices.
8
KF reagent
Automatic
Burette
Titration flask
Methanol
Platinum
electrodes
The titration apparatus should be protected from atmospheric moisture.
9
The close system
Iodine
Sulfur dioxide
Buffer
Solvent
I
2
SO
2
Imidazol
Methanol
10
HYDRANAL

Karl Fischer Reagents


Advantage
The HYDRANAL

reagents uses imidazole or


diethanolamine as a base, rather than noxious
pyridine. Imidazole and diethanolamine are both
safe and effective and guarantee reliable analyses.
Replacement of noxious pyridine with bases
that are both safer and more effective.
11
2 Steps
12
13
Standardization
USP34
14
Standardization
BP2012
15
Substance Remarks Water
content
Purified water Ideal if technician
knows how to proceed
100.00%
Certified water standards Not hygroscopic
Balance essential with
test certificate
10 mg/g &
1 mg/g
Fill MeOH in the titration flask to cover the electrodes.
Condition system to conditioning drift OK (<20 L/min).
Quickly add the water standard, accurately weighed containing
20 to 25 mg of water into the titration flask, stir and titrate until
the endpoint.
16
17
18
The water equivalent is NLT 80% of that indicated by
the supplier.
BP2012
19
20
F = the water equivalency factor of the Reagent, in mg/mL
KF = the limit or reasonable expected water content in
sample, in%
C = the used volume, in %, of the capacity of the buret
V = the buret volume, in mL
C is generally between 10%-100% for the instrument method endpoint.
FCV/KF
21
22
Calculate the water content of the specimen, in mg,
taken by the formula:
SF
Water content (%)
= SF x 100
mg of Test Preparation
23
Bivoltametry I
pol
= 50 A
Current applied to a double Pt electrode
During titration: Excess H
2
O
High voltage between the Pt wires
At the end of titration: Small excess of free iodine
Voltage decreases sharply
Drift in
l/min
Stop at 6 l/min
Enter the sample
Time in s
Basis Drift
e.g. 6 l/min
25
Water content of sample
(absolute content in g)
Maximal permitted
RSD%
< 500 (< 0.5 mg) Not reported
500-1000 (0.5-1.0mg) 5.0%
1000-2000 (1.0-2.0mg) 3.0%
2000-5000 (2.0-5.0mg) 2.0%
5000-15000 (5.0-15.0mg) 1.50%
0.0244 g of Standard water is equivalence to KFR
5.249 mL
Titer = 0.0244 x 1000 = 4.6485 mg/mL
5.249
0.1564 g of Lidocaine HCl is eq. to KFR 2.094 mL
water content(%) = 2.094 x 4.6485 x 100 = 6.22%
156.4
27
Limit USP34 (Lidocaine HCl) : between 5.0% and 7.0%
Conclusion: Pass
28

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