title: The interference of penicilloic acids with Karl Fischer titration of penicillins.
abstract: Phenoxymethylpenicilloic acid monohydrate was titrated with 12 different brands of Karl Fischer reagent. It was shown that only the four pyridine-containing reagents gave correct results for water content, providing that the sample solution was cooled in an ice bath or that the delay time of the amperometric end-point determination was 10 s instead of 30 s, as prescribed by the European Pharmacopoeia. The other reagents always gave results, which were too high. When these reagents were used to titrate the water in sodium amoxicillin, sodium carbenicillin or sodium ticarcillin the same conclusions could be drawn with regard to the accuracy of the results, the usefulness of the reagents and the reaction conditions. These penicillins may contain up to 9% penicilloic acids. The maximum relative error obtained with pyridine-free reagents was about 50% for ticarcillin. It has been confirmed that penicilloic acids interfere with Karl Fischer titration of water and that this interference is greatly dependent on the brand of reagent and on the reaction conditions.
authors.affiliation: Laboratorium voor Farmaceutische Chemie en Analyse van Geneesmiddelen, Faculteit Farmaceutische Wetenschappen, Katholieke Universiteit Leuven, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Hoebus
authors.forename: E
authors.initials: E
authors.lastname: Roets
authors.forename: J
authors.initials: J
authors.lastname: Hoogmartens
mesh_terms: D007202:Indicators and Reagents; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000032:analysis; D010406:Penicillins / Q000032:analysis*; D017186:Titrimetry / Q000379:methods
chemical_list: D007202:Indicators and Reagents; D010406:Penicillins; C008782:penicilloic acid; D010397:Penicillanic Acid