A chromatographic-densimetric method has been worked out, useful for identification and quantitative determination of eight cephalosporins: cefotaxime, cefuroxime, 1-acetoxyethyl ester of cefuroxime, cefadroxil, cefalexin, cefaclor and ceftriaxone. For three of them: acetoxyethyl ester, cefaclor and ceftriaxone, where the phenomenon of stereoisomerism occurs, validation of the method has been carried out. The method was used in subsequent examinations for determining not only the active substances content but also the content of their hydrolytic decomposition products. Conditions were established for chromatographical separation of rsomers of 1-acetoxyethyl ester of cefuroxime, cefaclor and ceftriaxone, with the use of a chiral modifier - B-cyclodextrine. The content of the individual isomers was determined in standard substances and m pharmaceutical preparations chosen at random from the circulation. The structure and identity of the separated isomers were verified with the 1H NMR and TLC methods in the case of 1-acetoxyethyl ester of cefuroxime and cefaclor, and with the TLC method in the case of ceftriaxone. Stability of the cephalosporins was examined in acidic solutions without as well as with the presence of P-cyclodextrine. Determination was carried out m solutions of different acidity, choosing for the later examinations such hydrochloric acid concentration at w ; hich the effect of B-cyclodextrine on the stability of the antibiotics examined was the largest (i.e. the differences between concentrations of the ingredient determined without and with the presence of B-cyclodextrine were the largest). It was found that the difference in concentrations of the antibiotics examined without and with the presence of B-cyclodextrine is the largest in the case of 1-acetoxyethyl ester of cefuroxime in HCI concentration of 0.1 mol/L, cefaclor in HCI concentration of 0.5 mol/L, and ceftriaxone in 1 mol/L HCI. While examining stability of 1-acetoxyethyl ester of cefuroxime, it was demonstrated that decomposition depends on incubation temperature. At 40°C, one product is formed, identified as cefuroxime, while at 50°C and 60°C - there are two additional products, one of which was identified as 2-[amino(carboxyl)methyl]-5-(hydroxymethyl )-3 ,6-dihydro-2H-I ,3-thiazine-4-carboxy lic acid. The structure of the next hydrolysis product failed to be validated with the 1H NMR method. The process of hydrolytic decomposition of cefaclor in acidic environment leads to formation of always two products, regardless of the incubation temperature. It was found that one of the hydrolysis products can be 7-amino-3-chloro-8-oxo-5-thia-I-azabiciclo[4.2.0]oct-2-eno-2-carboxylic acid, the other one being the remainder of phenyloglycine. In the case of ceftriaxone, we ; registered the forming of three hydrolysis products, one of which was identified as 2 [amino(carboxyl)methyl]-5-{[(6-hydroxy-2-methyl-5-oxo-2,5-dihydro-I ,2,4-triazine-3-yl)sulfany l]methy l }-3 ,6-dihydro-2H-1,3-diazine-4-carboxylic acid, the second one being probably an isomer of the compound identified, while the third one is a thiazole derivative. Based on the gained results of the decomposition reaction of 1-acetoxyethyl ester of cefuroxime, cefaclor and ceftriaxone in the solutions, it was established that it proceeds according to first-order reaction. The calculated values of t0.1 and t0.5, indicating decomposition time of the cephalosporins examined in solutions without any B-cyclodextrine content are significantly smaller than the analogous parameters obtained for examinations with a B-cyclodextrine content. This is confirmed with the thermodynamic values: activation energies (Ea) and activation enthalpies (~H++) calculated for the solutions examined. It was found that decomposition rate for all the antibiotics included in the research programme depended both on acid concentration, temperature and on incubation time. The strongest influence of p-cyclodextrine on the stability if the active substances was observed in the case of solutions of the antibiotic complexes with B-cyclodextrine in the tablet form, additionally enriched with B-cyclodextrine solution. Sma ; ller stability was found in solutions prepared with powdered tablet mass of the antibiotic with B-cyclodextrine as well as in complexes obtained by shaking the active substance with water solution of B-cyclodextrine. The fastest rate of the degradation process was observed in solutions without any addition of B-cyclodextrine (circa twice as fast).
Jul 21, 2022
Nov 21, 2012
6
0
http://dl.cm-uj.krakow.pl:8080/publication/1036
Edition name | Date |
---|---|
ZB-107999 | Jul 21, 2022 |
Dąbrowska, Monika
Żuchowski, Grzegorz
Krzyżanowska, Weronika
Niedzielska-Andres, Ewa