HomeTitration & Karl Fischer TitrationDetermination of Water Content in Benserazide Hydrochloride by Karl Fischer Titration

Determination of Water Content in Benserazide Hydrochloride by Karl Fischer Titration

Anita Piper, R&D Scientist


Product Group


General Information Concerning the Product Group

Pharmaceutical products are often characterized by complex formulations. Difficulties observed during Karl Fischer method for moisture determination are often caused by limited solubility. In some cases, side reactions have to be considered. In dependence of the composition and properties of the formulations, various measures are necessary for an undisturbed Karl Fischer water determination. In pharmaceutical guidelines (USP, Ph Eur, DAB) the Karl Fischer titration is described as a common method for water determination. For some substances, special procedures can be found. The determination of mass loss as a method for water determination is not recommended.

Special Information Concerning the Sample and Methods

Benserazide is a peripherally acting aromatic L-amino acid decarboxylase inhibitor that is unable to cross the blood-brain barrier. It is used in combination with L-DOPA in the management of Parkinson‘s disease and restless leg syndrome. Benserazide is not approved for this use in the US.

Chemical structure of Benserazide

DL-serine, 2-(2,3,4-trihydroxybenzyl)hydrazide

The purpose of this application note is to provide a rapid method to determine the water content, using a volumetric Karl Fischer titration method.

Benserazide hydrochloride is a strongly basic substance. Volumetric titration in combination with a buffer solution for strong bases is recommended and can lead to improved solubility and a more stable medium, leading to more reproducible results.

Karl Fischer Titration Method

One component volumetric Karl Fischer titration

Experimental Conditions

Karl Fischer Titration Procedure

  • The Karl Fischer reagent is connected to the burette. The titration medium is first placed into the titration cell and titrated dry by means of the titrant. The titer is determined using Aquastar® Water Standard 1% (1.88052).
  • Then the sample is added from a weighing boat (exact sample weight determination by weighing of weighing boat before and after addition) into the cell.
  • Start the titration. For complete extraction of the water from the sample a stirring time of at least 300 seconds is recommended.
  • Analysis of approximately 1,500 mg sample is possible before the Karl Fischer solvent needs to be changed.
  • It is recommended to test system performance using an appropriate standard for example Aquastar® Water Standard 1% (1.88052)

For other protocols on Karl Fischer titration see this overview.

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