HIRANUMA APPLICATION DATA

Watercontents

Karl Fischer Titrator

Data No.

KF9Apr. 19,
2018Drugs and Medicines – KF Coulometry
Thiamine Chloride Hydrochloride and Folic Acid

1. Abstract
Water contents of drugs and medicines could be determined by Karl Fischer coulometric titrator. In
coulometric titration, iodine of Karl Fischer reagent is generated by electrolysis and generated iodine
quantitatively reacts with water. Reaction formula is described below.
H2O ＋ I2 ＋ SO2 ＋ 3RN ＋ CH3OH → 2RN・HI ＋ RN・HSO4CH3
2RN・HI → I2 ＋ 2RN ＋ 2H＋ ＋ 2e－
When the moisture content is relatively high at the% level, the amount of sample added is as small as a few
10 mg. If the sample is in powder form, taking and adding samples with an “ultra-micro solid sampler” makes
measurement easy and accurate. An example for water contents measurements of thiamine chloridehydrochloride and folic acid performed by with ultra-micro solid sampler are introduced here. The
measurement method was determined with reference to Japanese Pharmacopeia.
Reference1) Japanese Pharmacopoeia Seventeenth Edition

2. Apparatus and Reagents(1) Apparatus
Titrator：

Hiranuma Karl Fischer Coulometric titrator

Electrolytic cell：Standard Cell without drain valve

Anode solution：

HYDRANAL Coulomat AG (Honeywell)

Cathode solution：

HYDRANAL Coulomat CG (Honeywell)(3) Sampling tool：

Ultra-micro solid sampler (P/N E730016-A, Fig.2.1)

AQ-series(P/N E324017-1)(2) Reagents

Fig.2.1 Ultra-micro solid sampler

3. Procedure(1) Fill 100 mL of anode solution and one ampoule of cathode solution into the electrolytic cell as shownin Fig.3.1.
(2) Set the ultra-micro solid sampler on the lid of cell as shown in Fig.3.2.
(3) Start blanking to attain stable background.
(4) Take sample into the capsule and accurately weigh it.
(5) Set the capsule on the sampler as pictured in the Fig.3.3.
(6) Pull the plate of sampler to introduce capsule into the cell.
(7) Start titration. Measurement parameter is shown in Table 4.1.
(8) Set sample weight to sample size.

Anode solution

Cathode solution

Fig.3.1. Preparation of the reagents.

Fig.3.2 Setting of ultra-micro solid sampler

Fig.3.3. Introduction of sample.

4. Parameters and results
Table 4.1. Parameters
Condition File
Cal ModeInterval Time
Current
S.TimerBlank Value
Unit Mode
Auto Interval
Minimum Count
Back Ground
Sample Size Input
Cell Type0:Sample weight (net)
X=(H2O-BLANK)/SIZE
30
MEDIUM
100
AUTO
05ON
Every Time
Standardsecminuggug

Table 4.2. Results of water content measurement in drugs and medicines
Samplesize (mg)Water(μg)

Watercontent (%)

Thiamine Chloride

33.2

1005.43.0283

Hydrochloride

30.3

912.7

3.0122

32.4

982.7

3.033012.5

814.97.8356

15.0962.9

7.7032

11.5880.9

7.6600SampleFolic acid

Statistics result

Remark

Avg.
SDRSD

3.0245%0.0109

%

0.4%

Avg.
SDRSD

7.7329%0.0915%1.2%

insoluble

insoluble

5. Note(1) Sampler, capsule and the other tools should be dried up well before use.
(2) After adding 10 to 20 capsules to the cell, open the cell lid and remove the capsule. Capsules can be
washed and reused.

(3) To measure 100 µg or less water detection, make sure stability of blanking. Low and stablebackground value is important factor for trace level of water measurement.
Keywords：Karl Fischer, Coulometric titration, Pharmacopeia, Solid