IODOMETRIC DETERMINATION OF CEFUROXIME BY THE POTASSIUM HYDROGENPEROXOMONOSULPHATE REACTION

Simple methods for oxidimetric determination of antibiotic Cefuroxime in the substance and in the powder for solution for injection, which are based on the S-oxidation reaction by potassium hydrogenperoxomonosulphate in a weak acidic medium to S-oxide with the subsequent determination of the residual oxidising agent by the iodometric method, have been developed. A triple potassium salt of Caro’s acid, 2KHSO5•KHSO4•K2SO4 was used as an oxidising agent. Quantitative oxidation of the Sulphur atom completes during the period that is less than 1 min. The mean recovery of the active ingredient in the substance of cefuroxime was 98.67%, RSD = 0.57% (δ = 0.33%). The mean recovery of the medicine “Cefuroxime”, 750 mg, is 782.8 mg, RSD = 0.97% (δ = 0.91%), which should be 680900 mg calculated with reference to dried substance. The LOQ is С = 0.05 mg mL-1. The advantages of the method proposed are the ability of analytical determination of cefuroxime by the biologically active part of the molecule, namely alicyclic Sulphur, good precision and accuracy of the results. The validation data obtained meet the requirements of the State Pharmacopoeia of Ukraine, they indicate the possibility of its introduction in the practice of analytical laboratories analysis, application during the stepwise control process of drug manufacturing or the quality control during equipment washing.

acid, is a derivative of 7-ADCC and belongs to semisynthetic cephalosporin β-lactam antibiotics of the ІI generation. The EPh and BP recommend to determine cefuroxime using the method of HPLC [3,6]. The classical iodometric titration method is long lasting and unreliable [1]. The extensive literature survey reveals several procedures of cefuroxime determination in medicines using liquid chromatography [12], capillary electrophoresis [8], polarography [2], and spectrofluorimetry [9]. A lot of spectrophotometric [4,5,11] and titrimetric [10,7] methods for quantitative determination of cefuroxime have been developed.
The aim of the study was to develop a new method for quantitative determination of cefuroxime in the substance and the powder for solution for injection by oxidimetry using potassium hydrogenperoxomonosulphate as an analytical reagent (KHSO 5 ).

Materials and Methods
A triple potassium salt of Caro's acid, 2KHSO 5 •KHSO 4 • K 2 SO 4 (the trade name -"Oxon ® " manufactured by DuPont), was used as an oxidising agent. The active substance is potassium hydrogenperoxomonosulphate, KHSO 5 . The choice of the reagent was determined by its rather high oxidative activity, Е 0 = 1.84 V, availability, and satisfactory solubility in water.  The medicine Cefuroxime, powder for solution for injection, 0.75, manufactured by "Lekchim-Kharkov", the batch 10712230412 was used.
The titrant volume was measured using a 10 mL microburette with the accuracy of ±0.01 mL.
Assay for cefuroxime in the powder for preparing the solution for injection. Dissolve 0.43 g (accurate weight) of the powder of the medicine with the known moisture content (w, %) in 70 mL of distilled water and dilute the volume to 100.00 mL. Transfer 10.00 mL into a 100 mL volumetric flask, add 10.00 mL of 0.02 Mol/L -1 KHSO 5 solution, dilute to the volume with distilled water, mix thoroughly and leave for 1 min. Then transfer 10.00 mL of the solution obtained into a flask for titration, add 1 mL of 0.1 Mol L -1 sulphuric acid solution and 1 mL of 5% potassium iodine solution. Titrate the iodine liberated with 0.02 Mol/L -1 of sodium thiosulphate solution (V, mL).
Simultaneously the control experiment was carried out under similar condition (without cefuroxime with the same amount of 0.02 Mol/L -1 of KHSO 5 solution (V 0 , mL).
The content of cefuroxime in the powder for solution for injection Х (g) was calculated by the formula: where: V 0 -is the volume of the standard 0.02 Mol/L -1 sodium thiosulphate solution used for titration in the control experiment, mL; V -is the volume of the standard 0.02 Mol/L -1 sodium thiosulphate solution used for titration in the experiment with cefuroxime, mL; К -is the correlation coefficient of the concentration for the standard 0.0200 Mol/L -1 sodium thiosulphate solution; Т -is the cefuroxime weight corresponding to 1.00 mL of the standard 0.0200 Mol/L -1 sodium thiosulphate solution, g/mL -1 ; 100 and 10 -are the volumes of the volumetric flask and aliquots of the solution taken for analysis, mL; m w -is the sample weight, g; m -is the average weight of the vial, g; w -is the moisture content in the medicine, %.
1.00 mL of the standard 0.0200 Mol/L -1 sodium thiosulphate solution correspond to 0.004244 g of cefuroxime (C 16 H 16 N 4 O 8 S), the medicine should contain 0.68-0.90 g calculated with reference to dried substance.

Results and Discussion
The peroxiacidic method proposed is based on the reaction of Cefuroxime oxidation by the excess of KHSO 5 with quantitative formation of the corresponding S-oxide in the acidic medium. The KHSO 5 excess was determined by the method of iodometric tirtation.
It has been determined that the redox interaction between cefuroxime and potassium hydrogenperoxomonosulphate occurs quantitatively and stoichiometrically: 1 Mol of KHSO 5 per 1 Mol of the medicine.
Quantitative oxidation of the Sulphur atom completed during the period that did not exceed 1 min by the method of iodometric titration.
The scheme of the S-oxidation reaction of cefuroxime using potassium hydrogenperoxomonosulphate is given in Fig. The results of quantitative determination of cefuroxime in the substance and in the medicine are given in Table. They show that the methods developed allow to determine the content of cefuroxime in the substance and the powder for solution for injection, 0.75 g, RSD = 0.57÷0.97%, δ = 0.3÷0.91%.
The Limit of Quantification (LOQ) is 0.05 mg mL -1 . The advantages of the method proposed are the ability of analytical determination of cefuroxime by the biologically active part of the molecule, namely alicyclic Sulphur, good precision and accuracy of the results. It does not require the use of expensive reference standards, toxic solvents and special equipment as in the HPLC method. It is simple and rapid in application.
CONCLUSIONS It has been proposed to use potassium hydrogenperoxomonosulphate as an analytical reagent for cefuroxime.
The methods for oxidimetric determination of the active ingredient in the substance and in Cefuroxime, powder for solution for injection, 0.75 g, which are based on the S-oxidation reaction by potassium hydrogen-  peroxomonosulphate in the acidic medium to the corresponding S-oxide with the subsequent determination of the residual oxidising agent by the iodometric method, have been proposed and developed (RSD = 0.57÷0.97%, δ = 0.3÷0.91%). The Limit of Quantification (LOQ) is 0.05 mg mL -1 .