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 this report, the suitability test of Japanese Pharmacopoeia Eighteenth Edition was performed for dextromethorphan hydrobromide monohydrate, also introduced in Application Data No. 11, with back-titration method. Please refer to Application Data No. 11 for the factor determination of titrants procedure and the repeatability of measurement results for dextromethorphan hydrobromide monohydrate.
In the pharmaceutical industry, ensuring the quality and efficacy of drugs and medicines is of utmost importance. Moisture content is a critical parameter to consider, as it can affect the stability and shelf life of pharmaceutical products. Karl Fischer (KF) titration is a widely used technique for accurate and precise determination of moisture content. In this article, we will discuss the suitability testing of drugs and medicines using KF volumetry and back-titration with the Karl Fischer Titrator AQV-300/MOIVO-A19, following the guidelines outlined in the Japanese Pharmacopoeia.
- Karl Fischer Volumetry: KF volumetry is a titration method used to determine the water content in samples. It involves the reaction between water and the Karl Fischer reagent, which contains iodine, sulfur dioxide, and a base. The Karl Fischer Titrator AQV-300/MOIVO-A19 is a specialized instrument that automates the KF volumetry process, providing accurate and reliable results.
- Back-Titration Method: Back-titration is a technique used when the sample contains substances that may interfere with the direct KF titration. It involves adding an excess amount of Karl Fischer reagent to the sample, allowing the water in the sample to react completely. The remaining unreacted Karl Fischer reagent is then back-titrated with a standard solution of water to determine the water content in the sample accurately.
Procedure:
Step 1: Sample Preparation:
- Follow the guidelines provided in the Japanese Pharmacopoeia for sample preparation.
- Weigh a representative portion of the drug or medicine sample using a precise analytical balance.
Step 2: KF Volumetry:
- Calibrate the Karl Fischer Titrator AQV-300/MOIVO-A19 according to the manufacturer’s instructions.
- Place the sample in a suitable container and introduce it into the titration cell of the titrator.
- Set the titration parameters on the instrument, including reagent volume, stirring speed, and endpoint determination method.
- Initiate the titration process, allowing the Karl Fischer Titrator AQV-300/MOIVO-A19 to automatically add the Karl Fischer reagent to the sample and determine the endpoint based on the electrochemical or visual detection method.
- Record the volume of Karl Fischer reagent used for titration.
Step 3: Back-Titration:
- Add an excess amount of Karl Fischer reagent to another portion of the sample, ensuring complete reaction with the water content.
- Prepare a standard solution of water with a known concentration.
- Back-titrate the excess Karl Fischer reagent in the sample with the standard solution of water until the endpoint is reached.
- Record the volume of the standard solution used for back-titration.
Step 4: Calculation of Water Content:
- Calculate the water content in the sample based on the volumes of Karl Fischer reagent used in the KF volumetry and back-titration steps.
- Apply the appropriate equations and conversion factors as specified in the Japanese Pharmacopoeia.
Suitability testing of drugs and medicines for moisture content using KF volumetry and back-titration with the Karl Fischer Titrator AQV-300/MOIVO-A19 is crucial to ensure their quality and stability. Following the guidelines outlined in the Japanese Pharmacopoeia, this analytical method provides accurate and reliable results. Proper instrument calibration, precise sample preparation, and adherence to the specific procedures outlined in the pharmacop