HIRANUMA APPLICATION DATA

Data No. B20

Automatic Titrator

Nov. 14,2018Standardization of perchloric acid in acetic acidwith potassium hydrogen phthalate

Drugs and Medicines

1. Abstract
Measurement method with perchloric acid - acetic acid standard solution is defined as a quantitative
determination method for each drug and medicine in Japanese Pharmacopoeia. Standardization of perchloric
acid - acetic acid standard solution with potassium hydrogen phthalate is also described there. This reportintroduces the standardization procedure that potassium hydrogen phthalate is dissolved in acetic acid, then it istitrated with perchloric acid - acetic acid standard solution. The factor of perchloric acid - acetic acid standard
solution is determined with potentiometric titration. 1 mol potassium hydrogen phthalate reacts with 1 molperchloric acid quantitatively on this titration (formula 1).

COOH

COOH+HClO4 →+KClO4･･･(1)

COOH

COOK

2. Configuration of instruments and reagents(1) Configuration of instruments
Main unit: Hiranuma Automatic Titrator

COM Series

Electrodes: Glass electrodeGE-101B**: Reference electrodeRE-201Z**Inner solution has to be changed to saturated sodium perchlorate inacetic acid.
**Glass-reference combination electrode GR-511BZ is also usable.
(2) Reagents
Titrant: 0.1 mol/L perchloric acid - acetic acid standard solution

Titration solvent: 50 mL of acetic acid (reagent grade)Standard sample: Potassium hydrogen phthalate (volumetric standard)

Inner solution: Saturated sodium perchlorate in acetic acid

3. Measurement procedure(1) Take about 0.3 g of potassium hydrogen phthalate into 100 mL beaker and weigh accurately to 0.1 mgdigits.
(2) Add 50 mL of acetic acid and dissolve sample by heating and stirring. After that, cool it down to room
temperature.
(3) Immerse the electrodes and titrate with 0.1 mol/L perchloric acid - acetic acid standard solution.
Additionally, perform the blank test with the same procedure of sample measurement.

4. Measurement conditions and results
Examples of titration conditions
Measurement of blank
Cndt No.
MethodBuret No.
Amp No.
D. Unit
S-Timer
C.P. mLT Timer
D.P. mLEnd Sens
Over mL
Max.Vol.

1
Auto
11mV
10000300
0.2
1.0sec
mL
sec
mL
mL
mL

ConstantNo.
SizeBlank
Molarity
FactorKL

1000.1000
000Unit
FormulaDigitsAuto In Pram.

mL
D
3Nong
mL
mol/L

Mode No.
Pre Int
Del K
Del Sens
Int Time
Int Sens
Brt Speed
Pulse

1700053216sec
mV
sec
mV

Measurement of potassium hydrogen phthalate
Cndt No.
MethodBuret No.
Amp No.
D. Unit
S-Timer
C.P. mLT Timer
D.P. mLEnd Sens
Over mL
Max.Vol.

2
Auto
11mV
10
8.0
30
0.2
300
0.0030

sec
mL
sec
mL
mL
mL

ConstantNo.
SizeBlank
Molarity
FactorKL
Unit
FormulaDigitsAuto In Pram.

200.0100
0.10000.9998204.224
1.000gmL
mol/L*Mode No.
Pre Int
Del K
Del Sens
Int Time
Int Sens
Brt Speed
Pulse

805053240sec
mVsec
mV

Fact2
S*F*1000/(K*M*(D-B))
Non* Factor = (Purity of potassium hydrogen phthalate (%)/100)

Measurement results
Measurement of blank

Measurement of potassium hydrogen phthalate

Number ofSize

Titrant

Number ofSize

Titrant

Measurement(g)

Volume (mL)

Measurement(g)

Volume (mL)

1-

0.010

10.2908

14.271

0.99832-0.01020.3068

15.061

0.997930.2956

14.526

0.9969Avg.
（Blank）

0.010 mL
Statistic
calculation

FactorAvg.

0.9977

SD0.001

RSD

0.072 %

Measurement of blank

Measurement of potassium hydrogen phthalate

Examples of titration curves

5. Note(1) Effect of water on perchloric acid titration
Water mixed in a measurement system affects to the reaction system of perchloric acid titration
because of the leveling effect, which results in a negative effect such as lowered quantitative performance or
getting less sensitivity around the end point. Therefore please take care not to mix water in the measurement
system. Reference electrode for non-aqueous titration should be prepared as described in the following item(2), because water of KCl solution commonly used as inner solution for reference electrode could be mixed in
the measurement system.
(2) Preparation of inner solution for reference electrodeThe inner solution of the reference electrode RE-201Z is filled with 4 M KCl aqueous solution whenpurchased. This inner solution have to be replaced to saturated sodium perchlorate in acetic acid solution forthis measurement. Replacement procedure is described below.
i) Prepare the saturated solution of sodium perchlorate in acetic acid with reagent grade.
ii) Discharge inner solution from reference electrode RE-201Z and wash inside it with water and thenacetic acid.
iii) Fill the prepared inner solution into reference electrode from the supply port.
iv) Cure the electrode for one day before use.
(3) Influence of experiment temperature on perchloric acid titration
Acetic acid used as a solvent for the titrant has a relatively large thermal expansion coefficient. Whenthe temperature changes by 1 °C, the titrant causes a volume change of 0.1 %. Factor titration and sample
measurement should be performed at the same room temperature as much as possible for accurate
measurement. (Please refer to application data B19 in regards to factor correction.)
Keywords：Drugs and medicines, Japanese pharmacopoeia, Perchloric acid titration, Standardization, Non-aqueoustitration, Potassium hydrogen phthalate*Some measurement would not be possible depending on optional configuration of system.