Karl Fischer & Potentiometric Titration Application Library
Drugs and Medicines – KF Volumetry, Back-Titration, Dextromethorphan Hydrobromide Monohydrate | Karl Fischer titrator AQV-300/MOIVO-A19
Water contents of drugs and medicines could be determined by Karl Fischer volumetric titrator. In volumetric titration, the titrant have a factor which means the ability to react with how many milligrams of 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.
There are two methods in KF volumetric titration, forward-titration and back-titration. Forward-titration is used in general. However, some of the sample should be measured by back-titration method according to Pharmacopeias. In back-titration method, firstly excess amount of KF titrant is added to the water contained in the sample, and then the remaining unreacted of KF titrant is titrated with water-in-methanol solution. Therefore, it is necessary to measure the factor not only KF titrant but also the water-in-methanol before the sample measurement.
An example for water contents measurements of dextromethorphan hydrobromide monohydrate performed by back-titration method is introduced here. The measurement method was determined with the reference to Japanese Pharmacopeia. Please refer to Application Data No. 22 for the suitability test of Japanese Pharmacopoeia eighteenth edition by the back titration method.
Reference
1) Japanese Pharmacopoeia Eighteenth Edition
There are two methods in KF volumetric titration, forward-titration and back-titration. Forward-titration is used in general. However, some of the sample should be measured by back-titration method according to Pharmacopeias. In back-titration method, firstly excess amount of KF titrant is added to the water contained in the sample, and then the remaining unreacted of KF titrant is titrated with water-in-methanol solution. Therefore, it is necessary to measure the factor not only KF titrant but also the water-in-methanol before the sample measurement.
An example for water contents measurements of dextromethorphan hydrobromide monohydrate performed by back-titration method is introduced here. The measurement method was determined with the reference to Japanese Pharmacopeia. Please refer to Application Data No. 22 for the suitability test of Japanese Pharmacopoeia eighteenth edition by the back titration method.
Reference
1) Japanese Pharmacopoeia Eighteenth Edition
Drugs and Medicines – KF Volumetry, Direct-Injection Propylene glycol and Glycerin | Karl Fischer titrator AQV-300/MOIVO-A19
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 Japanese Pharmacopeia.
Reference
1) Japanese Pharmacopoeia Seventeenth Edition
ASTM E203 : Standard Test Method for Water Using Volumetric Karl Fischer Titration
ASTM D4377 : Standard Test Method for Water in Crude Oils by Potentiometric Karl Fischer Titration
ASTM D890 : Standard Test Method for Water in Liquid Pine Chemicals
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 Japanese Pharmacopeia.
Reference
1) Japanese Pharmacopoeia Seventeenth Edition
ASTM E203 : Standard Test Method for Water Using Volumetric Karl Fischer Titration
ASTM D4377 : Standard Test Method for Water in Crude Oils by Potentiometric Karl Fischer Titration
ASTM D890 : Standard Test Method for Water in Liquid Pine Chemicals
Drugs and Medicines – KF Coulometry, Thiamine Chloride Hydrochloride and Folic Acid | Karl Fischer titrator AQ-300/MOICO-A19
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
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
Oil products – Fuel oil | Karl Fischer titrator AQ-300/MOICO-A19/EV-2000L
Water content of oil products are 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⁻
Generally the fuel oil does not interfere the Karl Fischer reaction and direct injection method could apply. Suitable anode solution is selected for dissolving oil samples.
It is known that some of the oil additives interfere Karl Fischer reaction. In that case, azeotropic distillation method with Oil evaporator is appropriate. Water is separated from oil sample by distillation and introduced to electrolytic cell with carrier gas.
ASTM D6304 : Standard Test Method for Determination of Water in Petroleum Products, Lubricating Oils, and Additives by Coulometric Karl Fischer Titration
H₂O ＋ I₂ ＋ SO₂ ＋ 3RN ＋ CH₃OH → 2RN・HI ＋ RN・HSO₄CH₃
2RN・HI → I₂ ＋ 2RN ＋ 2H⁺ ＋ 2e⁻
Generally the fuel oil does not interfere the Karl Fischer reaction and direct injection method could apply. Suitable anode solution is selected for dissolving oil samples.
It is known that some of the oil additives interfere Karl Fischer reaction. In that case, azeotropic distillation method with Oil evaporator is appropriate. Water is separated from oil sample by distillation and introduced to electrolytic cell with carrier gas.
ASTM D6304 : Standard Test Method for Determination of Water in Petroleum Products, Lubricating Oils, and Additives by Coulometric Karl Fischer Titration
Nitriles | Karl Fischer titrator AQ-300/MOICO-A19
Water content of Nitriles 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⁻
Nitriles do not interfere the Karl Fischer reaction and direct injection method could apply. Anode solution is selected in accordance with sample solubility. General use of anode solution contain methanol as solvent. When the sample like a long chain hydrocarbon has poor solubility in methanol, anode solution containing chloroform or hexanol or toluene is used.
H₂O ＋ I₂ ＋ SO₂ ＋ 3RN ＋ CH₃OH → 2RN・HI ＋ RN・HSO₄CH₃
2RN・HI → I₂ ＋ 2RN ＋ 2H⁺ ＋ 2e⁻
Nitriles do not interfere the Karl Fischer reaction and direct injection method could apply. Anode solution is selected in accordance with sample solubility. General use of anode solution contain methanol as solvent. When the sample like a long chain hydrocarbon has poor solubility in methanol, anode solution containing chloroform or hexanol or toluene is used.
Amines | Karl Fischer titrator AQ-300/MOICO-A19
Water content of amines 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⁻
The amines change anode solution pH to basic. In the case of an amine with stronger basicity than benzylamine (pKa = 9.34¹)) as a guideline, there are such effects as the end point becomes unclear. Therefore, when measuring a strongly basic amine, add a neutralizing agent to the anode solution beforehand to suppress the influence of undesirable effect caused by adding the sample. This application introduces an example for the water determination in cyclohexylamine(liquid), diethanolamine(liquid) and imidazole(solid). Reference
1) H. K. Hall, J. Am. Chem. Soc. (1957) 79 5441.
H₂O ＋ I₂ ＋ SO₂ ＋ 3RN ＋ CH₃OH → 2RN・HI ＋ RN・HSO₄CH₃
2RN・HI → I₂ ＋ 2RN ＋ 2H⁺ ＋ 2e⁻
The amines change anode solution pH to basic. In the case of an amine with stronger basicity than benzylamine (pKa = 9.34¹)) as a guideline, there are such effects as the end point becomes unclear. Therefore, when measuring a strongly basic amine, add a neutralizing agent to the anode solution beforehand to suppress the influence of undesirable effect caused by adding the sample. This application introduces an example for the water determination in cyclohexylamine(liquid), diethanolamine(liquid) and imidazole(solid). Reference
1) H. K. Hall, J. Am. Chem. Soc. (1957) 79 5441.
Ethers and Esters | Karl Fischer titrator AQ-300/MOICO-A19
Water content of Ethers and Esters are 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⁻
Ethers and esters do not interfere the Karl Fischer reaction and direct injection method could apply. Anode solution is selected from General-use or Oil in accordance with sample solubility. General-use anode solution contains methanol as solvent. When the sample has low solubility in methanol, the use of anode solution for oil is appropriate. One exception is a sample containing vinyl group, which reacts with KF reagent and interferes the titration. When fritless cell is used, cathode solution is not necessary.
H₂O ＋ I₂ ＋ SO₂ ＋ 3RN ＋ CH₃OH → 2RN・HI ＋ RN・HSO₄CH₃
2RN・HI → I₂ ＋ 2RN ＋ 2H⁺ ＋ 2e⁻
Ethers and esters do not interfere the Karl Fischer reaction and direct injection method could apply. Anode solution is selected from General-use or Oil in accordance with sample solubility. General-use anode solution contains methanol as solvent. When the sample has low solubility in methanol, the use of anode solution for oil is appropriate. One exception is a sample containing vinyl group, which reacts with KF reagent and interferes the titration. When fritless cell is used, cathode solution is not necessary.
Oil products | Karl Fischer titrator AQ-300/MOICO-A19/EV-2000L
Water content of Oil products are 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⁻
Kerosene and diesel oil do not interfere the Karl Fischer reaction and direct injection method could apply. Anode solution for Oil is selected to dissolve samples.
It is known that some of the oil additives interfere Karl Fischer reaction. In that case, azeotropic distillation method with Oil evaporator is appropriate. Water is separated from oil sample by distillation and introduced to electrolytic cell with carrier gas.
Mercaptanes and hydrogen sulfide in oil interfere Karl Fischer reaction. Since these side reactions occur quantitatively, water content result could be corrected with concentration of mercaptanes and hydrogen sulfide. 1 ppm of mercaptanes or hydrogen sulfide lead 0.3 ppm or 0.6 ppm higher water content respectively.
ASTM D6304 : Standard Test Method for Determination of Water in Petroleum Products, Lubricating Oils, and Additives by Coulometric Karl Fischer Titration
ASTM E1064 : Standard Test Method for Water in Organic Liquids by Coulometric Karl Fischer Titration
ASTM D4928 : Standard Test Method for Water in Crude Oils by Coulometric Karl Fischer Titration
H₂O ＋ I₂ ＋ SO₂ ＋ 3RN ＋ CH₃OH → 2RN・HI ＋ RN・HSO₄CH₃
2RN・HI → I₂ ＋ 2RN ＋ 2H⁺ ＋ 2e⁻
Kerosene and diesel oil do not interfere the Karl Fischer reaction and direct injection method could apply. Anode solution for Oil is selected to dissolve samples.
It is known that some of the oil additives interfere Karl Fischer reaction. In that case, azeotropic distillation method with Oil evaporator is appropriate. Water is separated from oil sample by distillation and introduced to electrolytic cell with carrier gas.
Mercaptanes and hydrogen sulfide in oil interfere Karl Fischer reaction. Since these side reactions occur quantitatively, water content result could be corrected with concentration of mercaptanes and hydrogen sulfide. 1 ppm of mercaptanes or hydrogen sulfide lead 0.3 ppm or 0.6 ppm higher water content respectively.
ASTM D6304 : Standard Test Method for Determination of Water in Petroleum Products, Lubricating Oils, and Additives by Coulometric Karl Fischer Titration
ASTM E1064 : Standard Test Method for Water in Organic Liquids by Coulometric Karl Fischer Titration
ASTM D4928 : Standard Test Method for Water in Crude Oils by Coulometric Karl Fischer Titration
Aromatic Hydrocarbon | Karl Fischer titrator AQ-300/MOICO-A19
Water content of Aromatic hydrocarbons are 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⁻
Aromatic hydrocarbons do not interfere the Karl Fischer reaction and direct injection method could apply. Anode solution is selected from General-use or Oil in accordance with sample solubility. General-use anode solution contains methanol as solvent. When the sample has low solubility in methanol, the use of anode solution for oil is appropriate. When fritless cell is used, cathode solution is not necessary.
H₂O ＋ I₂ ＋ SO₂ ＋ 3RN ＋ CH₃OH → 2RN・HI ＋ RN・HSO₄CH₃
2RN・HI → I₂ ＋ 2RN ＋ 2H⁺ ＋ 2e⁻
Aromatic hydrocarbons do not interfere the Karl Fischer reaction and direct injection method could apply. Anode solution is selected from General-use or Oil in accordance with sample solubility. General-use anode solution contains methanol as solvent. When the sample has low solubility in methanol, the use of anode solution for oil is appropriate. When fritless cell is used, cathode solution is not necessary.
Alcohols | Karl Fischer titrator AQ-300/MOICO-A19
Water content of Alcohols is 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⁻
Alcohols do not interfere the Karl Fischer reaction and direct injection method could apply. Anode solution is selected in accordance with sample solubility. General-use anode solution contains methanol as solvent. Alcohols with long carbon chain have low solubility in methanol. In that case, use of anode solution for oil is appropriate.
When fritless cell is used, cathode solution is not necessary.
H₂O ＋ I₂ ＋ SO₂ ＋ 3RN ＋ CH₃OH → 2RN・HI ＋ RN・HSO₄CH₃
2RN・HI → I₂ ＋ 2RN ＋ 2H⁺ ＋ 2e⁻
Alcohols do not interfere the Karl Fischer reaction and direct injection method could apply. Anode solution is selected in accordance with sample solubility. General-use anode solution contains methanol as solvent. Alcohols with long carbon chain have low solubility in methanol. In that case, use of anode solution for oil is appropriate.
When fritless cell is used, cathode solution is not necessary.
Hydrocarbon, Halogenated hydrocarbon | Karl Fischer titrator AQ-300/MOICO-A19
Water content of hydrocarbon and halogenated hydrocarbon 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⁻
Hydrocarbon and halogenated hydrocarbon do not interfere the Karl Fischer reaction and direct injection method could apply. Anode solution is selected in accordance with sample solubility. General use of anode solution contain methanol as solvent. When the sample like a long chain hydrocarbon have poor solubility in methanol, anode solution containing chloroform or hexanol or toluene is used. When fritless cell is used, cathode solution is not necessary.
H₂O ＋ I₂ ＋ SO₂ ＋ 3RN ＋ CH₃OH → 2RN・HI ＋ RN・HSO₄CH₃
2RN・HI → I₂ ＋ 2RN ＋ 2H⁺ ＋ 2e⁻
Hydrocarbon and halogenated hydrocarbon do not interfere the Karl Fischer reaction and direct injection method could apply. Anode solution is selected in accordance with sample solubility. General use of anode solution contain methanol as solvent. When the sample like a long chain hydrocarbon have poor solubility in methanol, anode solution containing chloroform or hexanol or toluene is used. When fritless cell is used, cathode solution is not necessary.
Determination of chloride ion in concrete | Autotitrator COM-A19
This report introduces an example of the determination of chloride ion in concrete. This measurement method is described in “Potentiometric titration method using chloride ion-selective electrode” of “JIS A 1154 Method of test for chloride ion content in hardened concrete”. Nitric acid is added to adjust the pH to 3 or less, and extract chloride ion with boiling. Cool to room temperature, filtrate to separate undissolved component and collect filtrated solution as sample. Chloride ion is determined by precipitation titration using a silver nitrate standard solution.
