HIRANUMA APPLICATION DATA

Watercontents

Karl Fischer Titrator

Data No. KF13

Apr. 19,2018

Drugs and Medicines – KF Volumetry, Powder Sample
Lactose hydrate and L-Histidine hydrochloride hydrate

1. Abstract
Water contents of drugs and medicines are usually determined by Karl Fischer volumetric titrator. In
volumetric titration, titrant have a factor 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 consumedtitrant volume within sample measurement.
This application introduces an example for the water determination in lactose hydrate and L-histidinehydrochloride hydrate with reference to Japanese Pharmacopeia. Sample is measured by direct injection intothe cell. When the solubility of the sample in methanol is not sufficient, use a mixed solvent of methanol andformamide as the titration solvent.
Reference
1) Japanese Pharmacopoeia Seventeenth Edition

2. Apparatus and Reagents(1) Apparatus
Titrator：

Hiranuma Karl Fischer Volumetric titrator

AQV-series

Titration cell：Standard Cell, without drain valve

P/N D327511-1

Powder funnel：

Less than 13 mm outer diameter of leg

Titrant：

HYDRANAL Composite 5 (Honeywell)

Methanol：

HYDRANAL Methanol (Honeywell)

Formamide：

HYDRANAL Formamide dry (Honeywell)Titration solvent：

Mixed solvent of methanol and formamide at a volume ratio of 2: 1

(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) Put a sample container, powder funnel and spoon on the balance. Record its read (S1 [g]).
(4) Open the glass stopper of titration cell lid to introduce the sample with powder funnel as shown inFig.3.2.
(5) Start titration. Measurement parameter is shown in Table 4.1.
(6) Weigh the sample container, powder funnel and spoon again and record its read (S2 [g]). The
difference of (S1-S2 [g]) is set as sample size.

Titration solvent

Fig.3.1 Preparation of the reagents

Fig.3.2 Introduction of sample with powder funnel

4. Parameters and results
Table 4.1 Parameters
Condition FileCal Mode

0:Sample weight (net)

Interval Time30sec

Max Volume

20

mL

Min Feed Vol.

0.01

mL

5min

S.Timer
KF Factor

5.7246

mg/mL

KF Buret No.

1

KF Speed(OUT)

12

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

Sample Size Input

Every TimeBlank Value0

Unit Mode

AUTO

E.P Detection

mVC.P Level

150

E.P Level

2Auto Interval

0

mL

mVg

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

Water(mg)Watercontent (%)

Lactose hydrate

0.99338.74

50.0335.0370Avg.

5.0202%1.0074

8.81

50.4345.0064SD

0.0155%1.0212

8.95

51.2355.0171

RSD

0.31%

L-Histidine hydrochloride

0.1227

1.84

10.5338.5844Avg.

8.5406%hydrate0.12301.84

10.5338.5634SD

0.0586%0.12701.88

10.7628.4740RSD

0.69%

Statistics result

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.
(4) The blanking might become unstable when time has passed since the solvents of methanol andformamide were mixed. The cause could be due to the ammonia generated by mixing solvent. Adding 3
g of benzoic acid to 50 mL of titration solvent improves the unstable state of blanking.
Keywords：Karl Fischer, Volumetric titration, Pharmacopeia