Stability of ceftiofur sodium and cefquinome sulphate in intravenous solutions was studied. Chromatographic separation and quantitative determination were performed by using a high-performance liquid chromatography with UV-DAD detection. During the stability study, poly(vinylchloride) minibags were filled with a solution containing 5 mg of ceftiofur sodium or cefquinome sulphate and diluted to 0.2 mg/mL with suitable intravenous solution depending on the test conditions. The solutions for the study were protected from light and stored at room temperature (22°C), refrigerated (6°C), frozen (−20°C) for 30 days, and then thawed at room temperature. A comparison of results obtained at 22°C and 6°C for the same intravenous solutions showed that temperature as well as components of solutions and their concentration had an influence on the stability of ceftiofur sodium and cefquinome sulphate. It was found that ceftiofur sodium and cefquinome sulphate dissolved in intravenous solutions used in this study may be stored at room temperature and at 6°C for up to 48 h.
The kinetic and thermodynamic parameters of degradation of doripenem were studied using a high-performance liquid chromatography method. In dry air, the degradation of doripenem was a first-order reaction depending on the substrate concentration. At increased relative air humidity, doripenem was degraded according to the autocatalysis kinetic model. The dependence ln k = f(1/T ) was described by the equations ln k = 5.10 ± 13.06 − (7576 ± 4939)(1/T ) in dry air and ln k = 46.70 ± 22.44 − (19,959 ± 8031)(1/T ) at 76.4% relative humidity (RH). The thermodynamic parameters E a , H =a , and S =a of the degradation of doripenem were calculated. The dependence ln k = f (RH%) was described by the equation ln k = (0.155 ± 0.077) × 10 −1 (RH%) − (3.45 ± 21.8) ×
Cefquinome sulfate is a veterinary, parenteral, fourth-generation cephalosporin with a methoxyimino-aminothiazolyl moiety into the acyl side chain and the quaternary quinoline group at position 3 of the cefem ring. Cefquinome sulfate is known to undergo degradation, which could be additionally increased by the presence of some critical factors such as temperature, relative air humidity, buffer components as well as hydrogen and hydroxide ions. The aim of this study was to evaluate the factors underlying the stability of cefquinome sulfate (CFQ) in aqueous solution and in the solid state taking into account general and specific acid-base hydrolysis in the pH range 0.45-10.48 at 343 K; the effect of temperature on the stability at 0% RH and an increased relative air humidity (RH = 76.4%); the influence of relative air humidity at 343 K (66.5-90%). To determine the observed rate constants, an isocratic HPLC-UV method was used. The three pK a values of cefquinome sulfate, kinetic (k obs. , k pH ), and activation parameters (E a , DH = , and DS = ) were determined.
The influence of pH and temperature on the stability of N-[(piperidine)methylene]daunorubicin hydrochloride (PPD) was investigated. Degradation was studied using an HPLC method. Specific acid-base catalysis of PPD involves hydrolysis of protonated molecules of PPD catalyzed by hydrogen ions and spontaneous hydrolysis under the influence of water zwitterions, unprotonated molecules, and monoanions of PPD. The thermodynamic parameters of these reactions, energy, enthalpy, and entropy, were calculated. Also, the stability of daunorubicin and its new amidine derivatives (piperidine, morpholine, pyrrolidine, and hexahydroazepin-1-yl) in aqueous solutions was compared and discussed.
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