HIRANUMA APPLICATION DATA

Automatic Titrator

Data No. B19

Apr. 19,2018

Purity determination for papaverinehydrochloride by perchloric aid titration

Drugs and Medicines

1. Abstract
Determination for papaverine hydrochloride is defined in Japanese Pharmacopoeia. Papaverinehydrochloride is used for improvement of vasodilatation and symptoms on gastritis, disease of biliary tract(gallbladder) system, acute arterial embolus, acute pulmonary embolism, peripheral circulatory failure, andinadequate coronary circulation.
The purity determination of papaverine hydrochloride using potentiometric titration with perchloric acid
titrant is introduced in this report. Sample is dissolved by heating with acetic anhydride / glacial acetic acidmixture and cooled to room temperature. After that, the titration is performed, 1 mol papaverine hydrochloride
reacts with 1 mol perchloric acid quantitatively.

Papaverine hydrochloride (C20H21NO4・HCl, FW:375.85)

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 inglacial acetic acid.
(2) Reagents
Titrant: 0.1 mol/L perchloric acid - acetic acid standard solution

Titration solvent: Mixture of glacial acetic acid and acetic anhydride (3:7, v/v)

Inner solution: Saturated sodium perchlorate in glacial acetic acid

3. Measurement procedure(1) Take about 0.5 g of sample into 200 mL beaker and weigh accurately to 0.1 mg digits.
(2) Add 100 mL of titration solvent and dissolve sample by heating and stirring. After that, cool it down toroom temperature.
(3) Immerse the electrode and titrate by 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.

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

ConstantNo.
SizeBlank
Molarity
FactorKL

1000.1
1.002
00UnitFormulaDigits
Auto In Pram.

mLD3Nong
mL
mol/L

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

1700053216sec
mVsec
mV

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

1Auto
11mV
10
830
0300
0.00
20sec
mL
sec
mL
mL
mL

ConstantNo.
SizeBlank
Molarity
FactorKL

100.100.1
1.002
375.850Unit
FormulaDigits
Auto In Pram.

gmL
mol/L

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

800053240secmVsecmV%(D-B)*K*F*M/(S*10)
4Non

Measurement results
Measurement of blank

Measurement of sample

Number ofSize

Titrant

Number of

Size

Titrant

PurityMeasurement(g)

Volume (mL)

Measurement(g)

Volume (mL)

(%)

1-

0.010

10.459312.216100.0830

2-

0.010

20.4815

12.76199.731030.4746

12.59599.8637

Avg.
（Blank）

0.010 mL
Statistic
calculation

Avg.

99.89 %

SD

0.18 %

RSD

0.18 %

Measurement of blank

Measurement of sample

Examples of titration curves

5. Note(1) Temperature correction of perchloric acid standard solution
This measurement determines the purity of the sample. Therefore, please pay attention for accurate
weighing, measurement of factor or blank. Especially, the factor determination of perchloric acid - acetic acidstandard solution should be regularly performed with potassium hydrogen phthalate. Acetic acid used as asolvent for the titrant has a relatively large thermal expansion coefficient. For example, a temperature changeof 1 °C on this titrant causes a volume change of 0.1 %. Factor titration and sample measurement should beperformed at the same room temperature as much as possible for accurate measurement.
When the temperature of the sample measurement is different from that of factor titration, assign thefollowing correction formula for titrant factor to the concentration calculation of sample.
F ：Corrected factor at sample titration
F0
F0：Factor at titrant factor determinationF
1＋α(t  t 0)
α ：Thermal expansion coefficient of titrant(Acetic acid＝1.07×10-3)
t ：Temperature at sample titration
t0 ：Temperature at titrant factor determination(2) Preparation of inner solution for reference electrodeThe inner solution of the reference electrode RE-201Z is filled with saturated KCl aqueous solution
when purchased. This inner solution have to be replaced to saturated sodium perchlorate in acetic acidsolution for this measurement. Replacement procedure is described below.
i) Prepare the saturated solution of sodium perchlorate in acetic acid with reagent grade of these.
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) Leave the electrode for one day before use.
Keywords：Drug, Papaverine hydrochloride, Japanese pharmacopoeia, Perchloric acid titration, Non-aqueous titration,
Saturated sodium perchloric acid - acetic acid solution*Some measurement would not be possible depending on optional configuration of system.