ABSTRACT
A micellar electrokinetic chromatography method for simultaneous assay of ticarcillin and clavulanic acid in Timentin i.v. injection preparation was developed. This method ensures excellent separation of both components of Timentin preparation. The validation of the method was performed, and specificity, reproducibility, precision and accuracy were confirmed. The detection and quantitative limits for Timentin were established in the concentrations 0.04 and 0.08 mg/ml, respectively. The elaborated technique was compared with two methods routinely used-UV and high performance liquid chromatography (HPLC). The obtained results and their statistical analysis proved the same precision of all methods, however, no significant differences were observed between CE and HPLC.
Subject(s)
Anti-Bacterial Agents/chemistry , Clavulanic Acid/chemistry , Clavulanic Acids/chemistry , Ticarcillin/chemistry , Anti-Bacterial Agents/analysis , Chromatography, High Pressure Liquid , Chromatography, Micellar Electrokinetic Capillary/methods , Clavulanic Acid/analysis , Clavulanic Acids/administration & dosage , Clavulanic Acids/analysis , Injections, Intravenous , Reproducibility of Results , Sensitivity and Specificity , Ticarcillin/administration & dosage , Ticarcillin/analysisABSTRACT
OBJECTIVE: To evaluate the physical and chemical stability of piperacillin sodium 3 and 4 g/100 mL and ticarcillin disodium 3 g/100 mL each admixed in NaCl 0.9% injection packaged in AutoDose Infusion System bags. DESIGN: Triplicate test samples of the penicillin antibiotics in NaCl 0.9% injection were packaged in ethylene vinyl acetate (EVA) plastic containers, AutoDose bags, designed for use in the AutoDose Infusion System. Samples were stored protected from light and evaluated at appropriate intervals for up to seven days at 23 degrees C and up to 30 days at 4 degrees C. Physical stability was assessed using turbidimetric and particulate measurement as well as visual inspection. Chemical stability was assessed by HPLC. RESULTS: All of the penicillin admixtures initially were clear when viewed in normal fluorescent room light and with a Tyndall beam. Measured turbidity and particulate content were low initially and exhibited little change in the ticarcillin disodium samples throughout the study. The piperacillin sodium samples exhibited small increases in measured haze throughout the study, but no accompanying increase in particulates > or = 1.04 microm was found. All samples were essentially colorless throughout the study. HPLC analysis found some decomposition in the samples. Piperacillin sodium exhibited a 9-10% loss after five days at 23 degrees C. In the samples stored at 4 degrees C, piperacillin sodium exhibited acceptable stability through 21 days of storage, but losses exceeded 10% after 30 days. Ticarcillin disodium exhibited a 7% loss after three days, but 14% after five days at 23 degrees C. Less than 7% loss occurred after 21 days, but 12% loss after 30 days at 4 degrees C. CONCLUSIONS: Piperacillin sodium and ticarcillin disodium exhibited physical and chemical stability consistent with previous studies on these drugs. The AutoDose Infusion System bags were not found to adversely affect the physical and chemical stability of these penicillin antibiotics.
Subject(s)
Drug Packaging , Penicillins/chemistry , Piperacillin/chemistry , Ticarcillin/chemistry , Chromatography, High Pressure Liquid , Drug Stability , Drug Storage , Infusions, Intravenous , Penicillins/administration & dosage , Piperacillin/administration & dosage , Temperature , Ticarcillin/administration & dosageABSTRACT
Aminoglycosides and penicillins chemically interact when they are combined in vitro or in vivo. The resulting adducts are considered to be biologically inactive. The major adducts formed in he interaction between tobramycin and ticarcillin have been recently isolated in pure form in our laboratory. On the basis of mass, infrared, and proton magnetic resonance spectra, the major adducts appeared 10 be amides formed by an attack of the beta-lactam carbonyl group of ticarcillin by an amino group of tobramycin. All other moieties of ticarcillin were intact except that the beta-lactam ring was opened and was rotated by 120-130 degrees . The minimum inhibitory concentrations (MICs) of the adducts, tobramycin, and ticarcillin were 20.0, 0.25, and 2.0 microg/mL for Staphylococcus aureus and Escherichia coli, and 160.0, 0.5, and 8.0 microg/mL for Pseudomonas aeruginosa. Thus, the major adducts possessed some antimicrobial activity, but not enough to be active in the treatment of infections. As shown by fluorescence polarization immunoassay (FPIA), the adducts demonstrate some cross-reactivity in the assay of tobramycin. However, it was insufficient to cause significant error in the measurement of tobramycin in human serum.
