COULOMETRIC DETERMINATION OF WATER IN THE SUBSTANCES OF THE ANTIBIOTIC CEPHALOSPORIN GROUP

The unique method of coulometric Karl Fischer (KF) titration was proposed for water determination in the substances of cefazolin sodium, cefuroxime sodium, cefotaxime sodium, ceftriaxone sodium, cefoperazone sodium, and cefepime dihydrochloride monohydrate sterile. Water was determined using an Expert -007 coulometer (Econix-Expert, Russia) at a current strength of 50 mA; the working solutions were KFI-anode and KFI-cathode (Akvametriya, Russia). A drying tube was filled with self-indicating silica gel (GOST 8984-75). The impermeability of a coulometric cell was controlled measuring the drift. The drift did not exceed 0.03 mg H2O/min. The accuracy of water determination was estimated by the standard solution HYDRANAL® – Check Solution 1.00 with a water content of 1.00±0.03 mg H2O/g (Riedel-de Haёn, Germany). The titration of cephalosporin sodium salts did not change pH of working medium or affect the stoichiometry of the KF reaction. The water content in the test substances was determined at three concentration levels covering the range of 70–130% as 100% level, and at 6 sample weights at the average level. The relative standard deviation of 1-2% was obtained. The mean relative bias was 1–2%. Coulometric KF titration for water determination is characterized by high precision and rapidity. This method needs no titrant standardization and it can be recommended for use in drug quality control laboratories and industrial pharmaceutical facilities.