HIRANUMA APPLICATION DATA

Watercontents

Karl Fischer Titrator

Data No.

KF
10V

Apr. 19,2018

Drugs and Medicines – KF Volumetry Direct-Injection
Propylene glycol and Glycerin

1. Abstract
Water contents of drugs and medicines could be determined by Karl Fischer volumetric titrator. In
volumetric titration, titrant have a titer which means the capacity to react with water per 1 mL of titrant. Factor
is pre-determined before sample measurement and water content of sample is calculated from consumed titrant
volume within sample measurement.
When the sample is liquid, generally sample is measured by direct injection into the cell. Dehydrated
methanol is used for titration solvent. The titration solvent may change to a composition suitable for dissolving
the sample.
Examples for water contents measurements of propylene glycol and glycerin performed by direct injection
method are introduced here. The measurement method was determined with reference to JapanesePharmacopeia.
Reference
1) Japanese Pharmacopoeia Seventeenth Edition

2. Apparatus and Reagents(1) Apparatus
Titrator：

Hiranuma Karl Fischer Volumetric titrator

Titration cell：Standard Cell

Titrant：HYDRANAL Composite 5 (Honeywell)Titration solvent：

HYDRANAL Methanol (Honeywell)(2) Reagents

3. Procedure(1) Fill 50 mL of titration solvent into the titration cell as shown in Fig.3.1.
(2) Start blanking to attain stable background.
(3) Wash the syringe with sample.
(4) Draw the sample into syringe and then weigh the syringe.
(5) Inject sample from rubber septum of titration cell as shown in Fig.3.2.
(6) Start titration. Measurement parameter is shown in Table 4.1.
(7) Weigh the syringe again and then set the difference of weight to sample size.

AQV-series

Titration solvent

Fig.3.1 Preparation of the reagents

Note(1) Do not touch the tip of needle totitration solvent.
(2) When injecting, set the tip ofneedle as below figure.

(3) Before pulling out the needle,
draw alittleairdripping of sample.

Fig.3.2 Injection of sampletoprevent

4. Parameters and results
Table 4.1 Parameters
Condition File
Cal Mode

0:Sample weight (net)
X=(H-b)×F×1000/SIZEInterval Time30sec

Max Volume20mL

Min Feed Vol.

0.01

mL0minS.Timer5.7614 mg/mL

KF Factor
KF Buret No.

1

KF Speed(OUT)

12mL/minKF Speed(IN)24mL/minBack GroundOFF

Sample Size Input

Every TimeBlank Value

0Unit Mode

AUTO

E.P DetectionmV
S,O,CE
150 mV
10 g

Solvent
C.P Level
E.P Level
Auto IntervalmL

Table 4.2 Results of water content measurement in drugs and medicines
SampleSamplesize(g)Titrant
volume(mL)

Water(mg)Watercontent(ppm)

Propylene glycol

2.0482

0.30

1.728

843.7

Avg.

860.9

ppm

2.0517

0.31

1.786

870.5

SD

14.9

ppm

1.9240

0.29

1.671

868.5

RSD

1.73%

6.9553

1.27

7.259

1043.7Avg.

1047.6ppm

7.0613
7.1525

1.29
1.32

7.374
7.545

1044.31054.9SDRSD

6.3
0.60ppm%

Glycerin

Statistics result

RemarkKF Factor
5.7614 mg/mL

KF Factor
5.7160 mg/mL

5. Note(1) Sampling tools should be dried up well before use.
(2) Purge and fill the titrant homogeneously into the buret.
(3) Organic solvents which have relatively high volume expansion coefficient are used as a constituent oftitrant. For accurate measurement, factor titration and sample measurement should be performed at thesame room temperature as much as possible.
Keywords：Karl Fischer, Volumetric titration, Pharmacopeia