Drugs and Medicines – KF Coulometry, Thiamine Chloride Hydrochloride and Folic Acid | Karl Fischer titrator AQ-300/MOICO-A19 - JM Science
HIRANUMA APPLICATION DATA Karl Fischer Titrator Data No. KF9 Apr. 19, 2018
Water contents Drugs 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 chloride hydrochloride and folic acid performed by with ultra-micro solid sampler are introduced here. The measurement method was determined with reference to Japanese Pharmacopeia. Reference
1) Japanese Pharmacopoeia Seventeenth Edition

2. Apparatus and Reagents

(1) Apparatus    
  Titrator : HIRANUMA Karl Fischer Coulometric titrator AQ-series or MOICO-A19
  Electrolytic cell : Standard Cell without drain valve (P/N E324017-1)
(2) Reagents    
  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)


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 shown in 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.

  • 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 Mode 0:Sample weight(net)  
  X=(H₂O-BLANK)/SIZE  
Interval Time 30 sec
Current MEDIUM  
S.Timer 10 min
Blank Value 0 ug
Unit Mode AUTO  
Auto Interval 0 g
Minimum Count 5 ug
Back Ground ON  
Sample Size Input Every Time  
Cell Type Standard  

 

Table 4.2. Results of water content measurement in drugs and medicines

Sample Sample
Size (mg)
Water
(μg)
Water
content (%)
Statistics resul Remark
Thiamine Chloride 33.2 1005.4 3.0283 Avg. 3.0245 % insoluble
Hydrochloride 30.3 912.7 3.0122 SD 0.0109 %  
  32.4 982.7 3.0330 RSD 0.4 %  
             
Folic acid 12.5 814.9 7.8356 Avg. 7.7329 % insoluble
  15.0 962.9 7.7032 SD 0.0915 %  
  11.5 880.9 7.6600 RSD 1.2 %  
             

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 stable background value is important factor for trace level of water measurement.

Keywords: Karl Fischer, Coulometric titration, Pharmacopeia, Solid
Hiranuma aquacounter aq-300 coulometric karl fischer titratorHiranuma aquacounter coulometric karl fischer titrator moico-a19Water contents

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