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In this study, electrochemical analysis of cefotaxime, one of the third-generation cephalosporins, the semisynthetic antibiotic group of the b-Lactam family, with an anodic pre-treated boron-doped diamond electrode (APT-BDDE) were investigated in a wide pH range. The cyclic voltametric (CV) and square-wave voltametric (SWV) techniques were applied for the rapid, sensitive, cheap, simple, and precise detection of CEF. The compound yielded two well-defined oxidation steps (Ia=1.1; IIa=1.5 V) in acidic, neutral, and alkaline media by employing SWV. Experimental conditions, namely pH, modulation amplitude, step potential, frequency, interference, and effect of scan rate were optimized. By employing SWV, there was a linear dependence of the oxidation peak current at +1.1 V and CEF concentration in the range of 1.0-20.0 µg mL-1 (2.1x10-6 - 4.2x10-5 mol L-1), with a detection limit of 0.22 µg mL-1 (4.6x10-7 mol L-1) in 0.1 mol L-1 phosphate buffer solution (pH 2.5). The practical applicability of the proposed method was tested with the quantification of CEF in the drug formulation. [ABSTRACT FROM AUTHOR]

A high-performance liquid chromatographic method (HPLC) with UV detection is described for determination of ceftriaxone sodium (CFX) and cefotaxime sodium (CFM) content in pharmaceutical industrial wastewater. These methods are based on the detection of these antibiotics via the formation of chelate complexes with Cu(II). The developed Liquid Chromatographic method offers symmetric peak shape, good resolution and reasonable retention time for both drugs. The removal percentage reached about 100 and 92.1% at pH 7.2 for CFX and CFM, respectively. In UV detection, the removal of the chelating antibiotics were based on forming of chelate complexes with Cu(II) which detected at λ max = 253 and 244 nm for CFX and CFM, respectively. Linearity, accuracy and precision were found to be acceptable over the concentration range of 5.99-59.86 µg mL -1 for CFX and 14.33-71.63 µg mL -1 for CFM. The proposed method can be used for the quality control of industrial wastewater containing CFX and CFM., (© 2024. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

Background: The increased use of cephalosporin antibiotics in the last few years as well as the detection of their residues in wastewater treatment plants and hospital wastewater poses a risk for infiltration of their residues into environmental water samples., Objective: A simplified, sensitive, and convenient solid-phase extraction (SPE) procedure coupled with either HPLC or fast HPLC methods with diode array detection was developed and validated to screen the residues of six different cephalosporin antibiotics: cefoperazone, cefipime, ceftazedime, ceftriaxone, cefdinir, and cefotaxime, along with amoxicillin, levofloxacin, and ciprofloxacin in water samples., Methods: An HPLC-diode array detector (HPLC-DAD) method and a fast HPLC method, based on a core-shell stationary phase, were developed for the fast screening of the antibiotic compounds. In addition, the SPE step was optimized to enable the extraction of the studied drugs with high accuracy of the recovered amounts of residues., Results: The method sensitivity was enhanced by the coupling of SPE with HPLC-DAD and fast HPLC to achieve low LODs; from 0.2 to 3.8 ng/mL and from 0.65 to 12.2 ng/mL, respectively. The developed methods were augmented by LC-MS/MS determination for confirmation of identity and quantity of any positively identified sample. The method was applied to the analysis of water samples collected from a rural site. In Addition, an example application of cleaning validation of cefotaxime-contaminated stainless-steel surfaces was provided., Conclusion: The method's simplicity and high sensitivity encourage its application in monitoring of antibiotic residues in different types of water samples such as environmental samples and samples from cleaning validation activities., Highlights: HPLC-DAD and fast HPLC methods were developed for separation of nine different antibiotics. The combination with the SPE procedure achieved low detection limits; from 0.2 to 3.8 ng/mL for SPE-HPLC-DAD and from 0.65 to 12.2 ng/mL for SPE-fast HPLC., (© The Author(s) 2023. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

In this research, we developed an online comprehensive two-dimensional liquid chromatographic (LC × LC) method hyphenated with high-resolution mass spectrometry (HRMS) for the non-targeted identification of poly- and perfluorinated compounds (PFASs) in fire-fighting aqueous-film forming foams (AFFFs). The method exploited the combination of mixed-mode weak anion exchange-reversed phase with a octadecyl stationary phase, separating PFASs according to ionic classes and chain length. To develop and optimize the LC × LC method we used a reference training set of twenty-four anionic PFASs, representing the main classes of compounds occurring in AFFFs and covering a wide range of physicochemical properties. In particular, we investigated different modulation approaches to reduce injection band broadening and breakthrough in the second dimension separation. Active solvent and stationary phase assisted modulations were compared, with the best results obtained with the last approach. In the optimal conditions, the predicted peak capacity corrected for undersampling was higher than three-hundred in a separation space of about 60 min. Subsequently, the developed method was applied to the non-targeted analysis of two AFFF samples for the identification of homologous series of PFASs, in which it was possible to identify up to thirty-nine potential compounds of interest utilizing Kendrick mass defect analysis. Even within the samples, the features considered potential PFAS by mass defect analysis elute in the chromatographic regions discriminating for the ionic group and/or the chain length, thus confirming the applicability of the method presented for the analysis of AFFF mixtures and, to a further extent, of environmental matrices affected by the AFFF., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Tilletia foetida causes wheat common smut disease with severe loss of yield production and seed quality. In this study, a low-cost, rapid, and efficient Agrobacterium tumefaciens-mediated transformation (ATMT) system for T. foetida mutagenesis was constructed: Transformants were screened with hygromycin B at 100 μg/ml, cefotaxime sodium concentrations with 200 μg/ml, Acetosyringone (AS) concentration at 200 μmol/l, 1 × 10 6  T. foetida hypha cells/ml, co-cultivation at 22 °C with 24 h and culture was incubated at 16 °C up to day 7. Fourteen transformants were randomly selected and confirmed using the specific primers to amplify the fragment of hygromycin phosphotransferase gene. At the same time, PCR analysis was performed to detect Agrobacterium tumefaciens Vir gene to eliminate false positives. The transformants were cultivated up to 8 generations on hygromycine B-containing complete medium (CM) and confirmed by PCR. The results indicated that 80% of T. foetida transformants were hygromycine B resistant. In conclusion, our analyses identified an efficient T-DNA insertion system for T. foetida and the results will be useful for further understanding the pathogenic mechanism via generation of the insertional mutants., (Copyright © 2019 Elsevier B.V. All rights reserved.)

We investigated the molecular characteristics and antimicrobial susceptibility of Clostridium difficile isolated from animals in China. We obtained 538 rectal swabs from pigs, chickens and ducks in 5 provinces during 2015 and 2016. C. difficile isolates were characterized by detection of toxin genes, multilocus sequence typing and ribotyping. And antimicrobial susceptibility testing was performed using the agar dilution method. Out of 538 samples, 44 (8.2%) were C. difficile positive with high prevalence in pigs (n = 31). Among these, 39 (88.6%) were toxigenic including 14 (31.8%) that were A+B+CDT+ and 13 (29.5%) A+B+. The remaining 12 (27.3%) were A-B+. We identified 7 ST types and 6 PCR ribotypes. The most predominant type was ST11/RT078 with toxin profile A+B+CDT+ and all were isolated from piglets with diarrhea. ST109 isolates possessed two different toxigenic profiles (A-B-CDT- and A-B+CDT-) and although it was not the most prevalent sequence type, but it was widely distributed between chickens, ducks and pigs in the 5 provinces. All C. difficile isolates were fully susceptible to vancomycin, metronidazole, fidaxomicin, amoxicillin/clavulanate and meropenem but retained resistance to 4 or 5 of the remaining antibiotics, especially cefotaxime, tetracycline, ciprofloxacin, cefoxitin. The RT078/ST11 isolates were simultaneously resistant to cefotaxime, tetracycline, cefoxitin, ciprofloxacin and imipenem. This is the first report of the molecular epidemiology of C. difficile isolated from food animals in China. We identified the epidemic strain RT078/ST11 as the predominate isolate among the animals we screened in our study., Competing Interests: The authors have declared that no competing interests exist.

The color grade, mainly introduced in the processes of semisynthesis and storage, is an important index used to evaluate the quality of cefotaxime sodium. Because the drug itself is prone to degradation under susceptible conditions, including those involving moisture, heat, ultraviolet light, acids, alkalis, and oxidants, and a series of degradation products as impurities are generated. In this study, the factors affecting color grade stability and the degradation mechanisms of cefotaxime sodium were investigated by designing different accelerated stability tests under the aforementioned conditions. The degradation extent was studied by using analytical methods, such as a solution color comparison method, ultraviolet spectrophotometry, and HPLC. The relationship between the color grade stability of cefotaxime sodium and its impurity profile has been explored, and a reasonable degradation mechanism has been proposed. The manufacturing conditions of inspection have been optimized, and a scientific basis for drug packaging, storage, and transportation conditions has been established. The results show that the color grade stability of cefotaxime sodium is related to the impurity profile to some degree, and the difference between the actual color and the standard color can reflect the levels of impurities to some extent., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Bacterial resistance to antibiotics is a growing phenomenon in the world. Considering the relevance of antimicrobials for population and the reduction in the registration of new antimicrobials by regulatory, proper quality control is required in order to minimize the spread of bacterial resistance and ensure the effectiveness of a treatment, as well as safety for the patient. Among the antimicrobials is cefotaxime, a drug belonging to third-generation cephalosporins, which is highly active against Gram-negative bactéria and is used to treat central nervous system infections such as meningitis and septicemia. Due to the critical importance of quality control in regard to drugs and pharmaceutical products, combined with bacterial resistance to antibiotics, this study aims to conduct a detailed review of analytical methods for cefotaxime. Using a critical review of literature, this paper describes the analytical methods published to quantify cefotaxime in different matrices; a large number of methods by HPLC and spectrophotometry were observed. Despite the advantages of the techniques, most methods reported have large environment and occupational impact, which enfatizes the need to adopt green procedures in quantifying cefotaxime.

The sensitivity of gas chromatography (GC) combined with the full evaporation technique (FET) for the analysis of aqueous samples is limited due to the maximum tolerable sample volume in a headspace vial. Using an acetone acetal as water scavenger prior to FET-GC analysis proved to be a useful and versatile tool for the analysis of high boiling analytes in aqueous samples. 2,2-Dimethoxypropane (DMP) was used in this case resulting in methanol and acetone as reaction products with water. These solvents are relatively volatile and were easily removed by evaporation enabling sample enrichment leading to 10-fold improvement in sensitivity compared to the standard 10μL FET sample volumes for a selection of typical high boiling polar residual solvents in water. This could be improved even further if more sample is used. The method was applied for the determination of residual NMP in an aqueous solution of a cefotaxime analogue and proved to be considerably better than conventional static headspace (sHS) and the standard FET approach. The methodology was also applied to determine trace amounts of ethylene glycol (EG) in aqueous samples like contact lens fluids, where scavenging of the water would avoid laborious extraction prior to derivatization. During this experiment it was revealed that DMP reacts quantitatively with EG to form 2,2-dimethyl-1,3-dioxolane (2,2-DD) under the proposed reaction conditions. The relatively high volatility (bp 93°C) of 2,2-DD makes it possible to perform analysis of EG using the sHS methodology making additional derivatization reactions superfluous., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The complexation reaction of cephalosporins namely cefotaxime (CTX), cefuroxime (CRX), and cefazolin (CEFAZ) with palladium (II) ions have been studied in water and DMF in 25 °C by the spectrophotometric methods. The method is based on the formation of yellow to yellowish brown complex between palladium (II) chloride and the investigated cephalosporins in the presence of sodium lauryl sulfate (SLS) as surfactant. The complexation process was optimized in terms of pH, temperature and contact time. The stoichiometry of all the complexes was found to be 2:1 (metal ion/ligand) for CTX, CRX, and 1:2 for CEFAZ. The stoichiometry of palladium (II)-cephalosporins was estimated by mole ratio and continuous variation methods and emphasized by the KINFIT program. These drugs could be determined by measuring the absorbance of each complex at its specific λmax. The results obtained are in good agreement with those obtained using the official methods. The proposed method was successfully applied for the determination of these compounds in their dosage forms., (Copyright © 2012 Elsevier B.V. All rights reserved.)

A simple, sensitive and rapid flow-injection chemiluminescence (CL) method has been developed for the determination of cefotaxime sodium based on the chemiluminescence reaction of cefotaxime sodium with ceric sulfate and rhodamine 6G in nitric acid solution. The concentration of cefotaxime sodium was proportional with the CL intensity in the range of 4×10(-8)-8×10(-6) mol L(-1). The detection limit (signal-to-noise ratio=3) was 1×10(-8) mol L(-1). Coupled to the technique of on-line microdialysis sampling, this method was successfully applied to study cefotaxime sodium-protein interaction. The drug and protein were mixed in different molar ratios in Ringer's solution, pH 7.4, and incubated at 37°C in a water bath. The microdialysis probe was utilized to sample the mixed solution at a perfusion rate of 5 μL min(-1) and the recovery of cefotaxime sodium under experimental condition was 16.2%. The data obtained by the present Microdialysis-Flow Injection Analysis-CL method was analyzed with the Scatchard analysis and Klotz plot. The estimated association constant (K) and the number of the binding sites (n) on one of BSA molecule were 5.94×10(4) M(-1) and 1.29 (Klotz equation), respectively., (Copyright © 2010 Elsevier B.V. All rights reserved.)

A rapid method for the determination of lipid classes with high sensitivity is described. The referenced Kendrick mass defect (RKMD) and RKMD plots are novel adaptations of the Kendrick mass defect analysis that allows for the rapid identification of members of a homologous series in addition to identifying the lipid class. Assignment of lipid classes by the RKMD method is accomplished by conversion of the lipid masses to the Kendrick mass scale and then referencing the converted masses to each lipid class. Referencing of the masses to a given lipid class is achieved by first subtracting the heteroatom and lipid backbone contributions to the mass defect, leaving behind the contribution to the mass by the fatty acid constituents. The final step in the referencing makes use of spacing differences in mass defects between members of the same Kendrick class to identify members of the lipid class being referenced. The end result of this is that a lipid belonging to the class being referenced will have an integer RKMD with the value of the integer being the degrees of unsaturation in the lipid. The RKMD method was able to successfully identify the lipids in an idealized data set consisting of 160 lipids drawn from the glyceride and phosphoglyceride classes. As a real world example the lipid extract from bovine milk was analyzed using both accurate mass measurements and the RKMD method.

An HPLC method for the separation of seven cephalosporins [Cefepime (CEP), ceftazidime (CTA), ceftizaxime (CTI), ceftriaxone (CTR), cefotaxime (COT), cefixime (CIX) and cefoperazone (COP)] in human plasma and amniotic fluid has been developed. Optimization of the chromatographic method was performed in three steps: a series of initial experiments followed by two sets of experiments based on different experimental designs. The initial experiments were performed to decide the basic analytical requirements of the method. Then screening experiment fractional factorial design was used in order to decrease the number of parameters by eliminating parameters which having insignificant effect on responses. The parameters having significant effect were further optimized through a full factorial design. Having studied two responses (retention times and resolutions), a desirability function that assess the responses together, was used to find experimental conditions where the system generated desirable results. The desirable results were obtained with XTerra C18 (250 mm x 4.6mm, 5 microm i.d.) column, 40 mM phosphate buffer, pH 3.2, 18% MeOH, 0.85 mL min(-1) flow rate and 32 degrees C column temperature. Gradient elution with MeOH was applied. A simple and efficient solid-phase extraction was applied for the preparation of plasma and amniotic fluid samples. The validation parameters of the method were evaluated in accordance with ICH guideline. The method validated was applied to the analysis of CEP and COP in maternal venous, fetal venous and fetal arterial plasma, and to the analysis of CIX in maternal venous plasma and amniotic fluid.

Aim: To investigate the effect of Chai-Qin-Cheng-Qi Decoction (CQCQD) on cefotaxime (CTX) concentration in pancreas of rats with acute necrotizing pancreatitis (ANP)., Methods: Sixty healthy male Sprague-Dawley rats were divided randomly into an ANP group (ANP model + CTX, n = 20), treatment group (ANP model + CTX + CQCQD, n = 20) and control group (normal rats + CTX, n = 20). ANP models were induced by retrograde intraductal injection of 3.5% sodium taurocholate (1 mL/kg), and the control group was injected intraductally with normal saline. All rats were injected introperitoneally with 0.42 g/kg CTX (at 12-h intervals for a continuous 72 h) at 6 h after intraductal injection. Meanwhile, the treatment group received CQCQD (20 mL/kg) intragastrically at 8-h intervals, and the ANP and control group were treated intragastrically with normal saline. At 15 min after the last CTX injection, blood and pancreas samples were collected for the determination of CTX concentration using validated high-performance liquid chromatography. Pathological changes and wet-to-dry-weight (W/D) ratio of pancreatic tissue were examined., Results: Serum CTX concentrations in three groups were not significantly different. Pancreatic CTX concentration and penetration ratio were lower in ANP group vs control group (4.4 +/- 0.6 microg/mL vs 18.6 +/- 1.7 microg/mL, P = 0.000; 5% vs 19%, P = 0.000), but significantly higher in treatment group vs ANP group (6.4 +/- 1.7 microg/mL vs 4.4 +/- 0.6 microg/mL, P = 0.020; 7% vs 5%, P = 0.048). The histological scores and W/D ratio were significantly decreased in treatment group vs ANP and control group., Conclusion: CQCQD might have a promotive effect on CTX concentration in pancreatic tissues of rats with ANP.

Cefotaxime enantiomers have specific effects on Gram-negative bacteria. For quality control of cefotaxime it was necessary to establish a method for enantioseparation by capillary zone electrophoresis (CZE) using cyclodextrin (CD) as a chiral selector. The effects of various parameters on enantioseparation were studied. A fused silica capillary (40 cm effective length x 75 microm ID) was used. The cefotaxime enantiomers were separated on the baseline under conditions of 0.5 mmol/L CM-beta-CD, 75 mmol/L NaH2PO4 buffer at pH 7.0 using UV detection at 280 nm. Applied voltage and capillary temperature were 20 kV and 25 degrees C, respectively. Under these conditions for enantioseparation, linear calibration curves were obtained in the range 2 approximately 160 microg/mL. The limit of detection for both isomers was less than 0.5 microg/mL. The method was used for analysis of pharmaceutical preparations (dosage forms) of cefotaxime from various factories. A simple and specific CZE method was successfully demonstrated for the separation of cefotaxime enantiomers. The enantioseparation method should be established and this method should be used to control the quality of cefotaxime.

Cefotaxime a third generation cephalosporin drug estimation in nanomolar concentration range is demonstrated for the first time in aqueous and human blood samples using novel Schiff base octahedral Zn(II) complex. The cefotaxime electrochemistry is studied over graphite paste and Zn(II) complex modified graphite paste capillary electrodes in H(2)SO(4) (pH 2.3) using cyclic voltammetry and differential pulse voltammetry. Cefotaxime enrichment is observed over Zn(II) complex modified graphite paste electrode probably due to interaction of functional groups of cefotaxime with Zn(II) complex. Possible interactions between metal complex and cefotaxime drug is examined by UV-vis and electrochemical quartz crystal microbalance (EQCM) techniques and further supported by voltammetric analysis. Differential pulse voltammetry (DPV) with modified electrode is applied for the determination of cefotaxime in acidified aqueous and blood samples. Cefotaxime estimation is successfully demonstrated in the range of 1-500 nM for aqueous samples and 0.1-100 microM in human blood samples. Reproducibility, accuracy and repeatability of the method are checked by triplicate reading for large number of samples. The variation in the measurements is obtained less than 10% without any interference of electrolyte or blood constituents.

Acidity constants of six cephalosporin antibiotics, cefalexin, cefaclor, cefadroxil, cefotaxim, cefoperazon and cefoxitin are determined using capillary zone electrophoresis (CZE) and pH-potentiometric titrations. Since CZE is a separation method, it is not necessary for the samples to be of high purity and known concentration because only mobilities are measured. The effect on determination of dissociation constants of different matrices (serum, 0.9% NaCl, fermentation matrix) was examined. The advantages of CZE can be utilized in those fields where potentiometry has limitations (sample quantity, solubility, purity, simultaneous determinations), although pK(a) values that are close to each other can be determined by potentiometry with more accuracy.

An efficient HPLC method for the compatibility study of cefotaxime with tinidazole in glucose injection is described, which has been developed for the simultaneous determination of cefotaxime and tinidazole in glucose injection. The appearance and pH value of the mixed solution were investigated and the concentrations of cefotaxime and tinidazole were determined by RP-HPLC with an Agilent ZORBAX Eclipse XDB-C8 column, gradient elution and dual wavelength detection on diode-array-detector (DAD) at room temperature (20 degrees C) within 24 h. It was found that the resulting appearance and pH value of the mixed solution showed slight changes, on the other hand, the quantity of cefotaxime decreased significantly. The results show that the mixed solution of cefotaxime with tinidazole in glucose injection must be used within 8 h in clinical due to the possible degradation of cefotaxime in tinidazole glucose injection. This study provides a convenient method for rational use of compatible drugs in clinical practice.

Ionization constants of three cephalosporin antibiotics, cefetamet (CEF), cefotaxime (CFX) and ceftriaxone (CFTR) are determined using pH-potentiometric titrations at I=0.1 M (NaCl) and t=25 degrees C. Cefetamet and cefotaxime have three ionization groups: carboxylic, amide and aminothiazole. Besides those three, ceftriaxone possesses an hydroxytriazinone group as new and additional ionization center. In acid medium two overlapping acid-base processes are occurring with acidity constants being: pK1 2.93 (COOH) and pK2 3.07 (aminothiazole) for cefetamet, and pK1 2.21 (COOH) and pK2 3.15 (aminothiazole) for cefotaxime. In the case of ceftriaxone the situation is even more complicated, three overlapping processes coexist with pK1 2.37 (COOH), pK2 3.03 (aminothiazole) and pK3 4.21 (hydroxytriazinone). Protolysis of amide group is happening in the alkaline medium as completely separated process from those in acid medium. The acidity constants which correspond to amide group are pK3 10.65 (CEF), pK3 10.87 (CFX) and pK4 10.74 (CFTR). The influence of the C3 substituent on the dissociation process of the neighboring ionization group, particularly carboxylic group, was considered. The differences in acidity of CEF, CFX and CFTR (pK1: 2.93, 2.21 and 2.37, respectively) are likely to be caused by the stereoelectronic properties of substituents in the beta-position to the carboxylic group due to the combined inductive, hyperconjugative and resonance effects.

A simple and reproducible spectrophotometeric method for the assay of cefotaxime sodium, cefuroxime sodium, and ceftriaxone disodium with metol-chromium(VI) reagent has been developed. The procedure is based on direct oxidation of metol by potassium dichromate in presence of drug in acidic medium and subsequent formation of ternary complex. Beer's law is obeyed in the range 0.2-28 microg ml(-1) at lambdamax 520 nm. For more accurate analysis, Ringbom optimum concentration range is found to be 0.8-26.5 microg ml(-1). The molar absorptivity and Sandell sensitivity were calculated. Six replicate analysis of solutions containing seven different concentrations of the examined drugs were carried out and gave a mean correlation coefficient < or =0.9996; the factors of the regression line equation for the three cephalosporins were calculated. The proposed method was applied to the determination of the examined drugs in pharmaceutical formulations and the results demonstrated that the method is equally accurate, precise, and reproducible as the official methods.

The manufacturing and storage of cefotaxime produces different impurities of various concentrations, which may influence the efficacy and safety of the drugs. Because no report of toxicity data is available on the impurities of cefotaxime, the present acute and genotoxicity studies were designed and conducted to provide the information for establishing the safety profile and qualification of the dimeric impurity. Histidine-requiring mutants of Salmonella typhimurium TA97a, TA98, TA100, TA102, and TA1535 strains, with or without metabolic activation (S-91, were used for point-mutation tests. Neither increase in numbers of revertants, indicative of mutagenic activity, nor inhibition of bacterial growth, indicative of cytotoxicity, was observed when the dimeric impurity of cefotaxime at concentrations of 0.62, 1.85, 5.56, 16.67, and 50 microg/plate was incorporated into plates containing S. typhimurium bacterial strains. Cultures of Chinese hamster ovary (CHO) cells at a cell density of 2 x 10(5) cells per culture were exposed to the dimeric impurity of cefotaxime at the concentration of 11.25, 22.5, and 45 mg per culture, with or without metabolic activation, and harvested at 18 h after exposure. No chromosomal aberrations in the cultured mammalian cells were recorded. Acute intramuscular administration of the dimeric impurity of cefotaxime in Sprague-Dawley rats did not result in any clinical signs and gross pathological changes up to 2000 mg/kg-body weight. The results of these studies indicated that the dimeric impurity of cefotaxime is nonmutagenic in Ames test, nonclastogenic in vitro, and acutely nontoxic in rats.

Derivative spectrophotometry (ratio-spectra 1st- and 2nd-derivative and zero-crossing 2nd-derivative techniques) was applied for the determination of some cephalosporins in two component mixtures. Cefotaxime sodium salt (C(16)H(16)O(7)N(5)S(2)Na) and cefadroxil monohydrate (C(16)H(17)N(3)O(5)S.H(2)O) were examined. In all procedures, the calibration plots are linear up to 43 microg/ml of each antibiotic, with r ranging from 0.9997 to 0.9999. In the ratio-spectra method, the measurements were taken at 239.5 and 291.5 nm (cefotaxime, 1st-derivative), 238 and 283 nm (cefadroxil, 1st-derivative), 284 and 303 nm (cefotaxime, 2nd-derivative), and 229.5 and 245.5 nm (cefadroxil, 2nd-derivative). Detection limits at P=0.05 level of significance, calculated by a statistical treatment of calibration data, ranged from 0.15 to 0.58 microg/ml. LOD and LOQ ranged, respectively, from 0.19 to 0.51 and from 0.63 to 1.70 microg/ml. By the zero-crossing 2nd-derivative method, lines of regression are linear at 257 and 279 nm (cefotaxime) and 242 and 296 nm (cefadroxil). Detection limits from 0.28 to 0.51 microg/ml. LOD and LOQ from 0.27 to 0.41 and from 0.90 to 1.37 microg/ml, respectively. All the samples were tested for stability in solution and in the course of actual analysis, up to 80 h from their preparation. The developed derivative spectrophotometric methods were applied to synthetic mixtures and the RSD values ranged between 0.05 and 1.35% (ratio-spectra technique) and 0.01 and 1.07% (zero-crossing technique). The methods were also applied to vials and tablets for these drugs. The recoveries obtained were between 100.9 and 102.4% (ratio-spectra) and between 99.8 and 102.0% (zero-crossing). The procedures are simple, rapid, and did not require any preliminary separation or treatment of the samples. Instrumentation commonly available was utilised. The cephalosporins analysed are frequently used antibiotics of relevant clinical and pharmacological importance; hence this work would be of interest for the readers of journals devoted to pharmaceutical and biomedical analysis.

Cefotaxime sodium (CX) and Ceftazidime pentahydrate (CZ) are peptidomimetic cephalosporins (CPS) which exist as zwitterionic compounds at physiological pH and because of this reason they are not absorbed appreciably on peroral administration. The permeability of these compounds can be increased transiently by altering membrane characteristics of absorptive epithelium by use of sorption promoters (SPs). In present work a simple validated HPLC method utilizing isocratic mobile phase and having short retention times for CX and CZ is developed which can be used to monitor their concentrations in Kreb's Ringer Bicarbonate (KRB) solution in in vitro intestinal sac absorption model. The same was utilized to determine apparent permeability coefficients and absorption profiles of CPS by modified Wilson-Wiseman method. The CPS were analysed by the reverse phase HPLC method using Shim-pack C18 column. The mobile phase used was of isocratic composition with phosphate buffer (pH 7.0, 3.5 g/l of KH(2)PO(4) dissolved in 0.03 M Na(2)HPO(4).2H(2)O) and methanol in proportion 85:15 for CZ and 70:30 for CX. The flow rate was 1 ml/min and quantitative determinations were carried out at 254 nm at 25 degrees C. The method was found specific because none of the proposed SPs, components of KRB and intestinal sac artefacts interfered with the drug peaks. The drug concentration versus area under peak relationship was found to be linear in concentration range of 0.25-20.0 microg/ml. The recovery studies, intraday variation, interday variation and interanalyst variation were within statistical limits. The limit of detection (LOD) was 95.0 and 100.0 ng/ml for CZ and CX, respectively. The limit of Quantitation (LOQ) was 240.0 and 250.0 ng/ml for CZ and CX, respectively. The proposed method was found to be rapid and selective and hence applied for continuous monitoring of CPS in in vitro intestinal sac absorption studies.

A flow-injection spectrophotometric method is described for the determination of cefadroxil (I) and cefotaxime (II). The method is based on the hydrolysis of the cephalosporin with sodium hydroxide whereby the sulfide ion is produced. The latter is allowed to react with N,N-diethyl-p-phenylenediamine sulfate (N,N-DPPD) and Fe (III), and the blue color produced is measured at 670 nm (method A). Linear calibration graphs are obtained in the range 36.34-109.2 and 95.48-477.4 microgml(-1) for I and II, respectively. The experimental limits of detection (three times the noise signal) are 0.036 and 0.048 microgml(-1) for I and II, respectively. The total flow-rate is 5.3 ml min(-1) for both drugs. Alternately, the sulfide ion produced is allowed to react with p-phenylenediamine dihydrochloride (PPDD) and Fe (III), and the violet color produced is measured at 597 nm (method B). Linear calibration graphs are obtained in the range 0.5-400 and 0.5-450 microg ml(-1) for I and II, respectively. The limits of detection are 0.4 and 0.2 microg ml(-1) for I and II, respectively. The total flow-rate is 3 ml min(-1) for both drugs. The methods have been successfully applied to the analysis of some pharmaceutical formulations, particularly of the injection and capsule types. The relative standard deviation (RSD) (n = 10) at the 50 and 100 microg ml(-1) levels of I and II were 0.83-0.77 and 0.9-0.8% with N,N-DPPD and PPDD as reagents, respectively. Recoveries were quantitative; the results obtained agreed with those obtained by other reported methods.

The stability of the lyophilized substance of cefodizime disodium was investigated. The test for the stability in solid state with and without presence of humidity was arried out by the HPLC method. Kinetic and thermodynamic parameters of the decomposition reaction were calculated.

A simple but effective coupling of microdialysis and microbore liquid chromatograph with UV detection technique was applied to the simultaneous studying of the pharmacokinetics of cefotaxime in both the peripheral compartment and central nervous system. The mobile phase consisted of methanol-100 mM monosodium phosphoric acid (25:75, v/v, pH 5.5) pumped through a C18 microbore column at a flow-rate of 0.05 ml/min. Detection of cefotaxime was set at a UV wavelength of 254 nm. Microdialysis probes were inserted into the jugular vein and striatum of the rat. Following stabilization of microdialysate levels, rats received cefotaxime (20 mg/kg, i.v., n=6) via the femoral vein, and complete concentration versus time profiles for blood and striatum were constructed. The results indicated that cefotaxime rapidly (within 10 min) entered the extracellular fluid of brain striatum following intravenous administration. Noncompartmental pharmacokinetics analysis indicated that the area under the concentration versus time ratio of cefotaxime in rat brain and blood was 6.9%, suggesting appreciable blood-brain barrier penetration. The method was relatively simple, imposed minimal physiological perturbance as it involved no body fluid consumption and sampled in particular protein-unbound drugs, generally believed to be the active fraction.

A capillary zone electrophoresis method is proposed for the purity determination of nine cephalosporin drugs. A background electrolyte comprising of either 20 mmol/L pH 9.20 borate buffer or 20 mmol/L pH 6.86 phosphate buffer was used for most drugs studied except for cefaloridine which formed neutral molecules at these pH values. For it 50 mmol/L pH 2.05 phosphate buffer was used instead. Internal normalization method was employed for quantitation. The method is simple, rapid and versatile. Analysis was completed within 8 min. The merits and limitations of the method were also discussed.

Two sensitive spectrophotometric and atomic absorption spectrometric procedures are developed for the determination of certain cephalosporins (cefotaxime sodium and cefuroxime sodium). The spectrophotometric methods are based on the charge-transfer complex formation between these drugs as n-donors and 7,7,8,8-tetracyanoquinodimethane (TCNQ) or p-chloranilic acid (p-CA) as pi-acceptors to give highly coloured complex species. The coloured products are measured spectrophotometrically at 838 and 529 nm for TCNQ and p-CA, respectively. Beer's law is obeyed in a concentration range of 7.6-15.2 and 7.1-20.0 microg x ml(-1) with TCNQ, 95.0-427.5 and 89.0-400.5 microg x ml-1 with p-CA for cefotaxime sodium and cefuroxime sodium, respectively. The atomic absorption spectrometric methods are based on the reaction of the above cited drugs after their alkali-hydrolysis with silver nitrate or lead acetate in neutral aqueous medium. The formed precipitates are quantitatively determined directly or indirectly through the silver or lead content of the precipitate formed or the residual unreacted metal in the filtrate by atomic absorption spectroscopy. The optimum conditions for hydrolysis and precipitation have been carefully studied. Beer's law is obeyed in a concentration range of 1.9-11.4 and 1.78-8.90 microg x ml(-1) with Ag(I), 14.2-57.0 and 13.3-53.4 microg x ml-1 with Pb(II) for cefotaxime sodium and cefuroxime sodium, respectively (for both direct and indirect procedures). The spectrophotometric and the atomic absorption spectrometric procedures hold well their accuracy and precision when applied to the analysis of cefotaxime sodium and cefuroxime sodium dosage forms.

The objective of this investigation was to develop a HPTLC method for the determination of ceftriaxone, cefixime and cefotaxime, cephalosporins widely used in clinical practice. High performance TLC of cephalosporins was performed on pre-coated silica gel HPTLC plates with concentrating zone (2.5 x 10 cm) by development in mobile phase ethyl acetate-acetone-methanol-water (5:2.5:2.5:1.5 v/v/v/v). A TLC scanner set at 270 nm was used for direct evaluation of the chromatograms in reflectance/absorbance mode. The calibration curves were established as dependence of peak height (linear and polynomial regression) and peak area (polynomial regression) versus ng level (125-500 ng for all cephalosporins investigated). Relative standard deviations obtained from calibration curves was compared. Precision (RSD: 1.12-2.91% (peak height versus ng) and RSD: 1.05-2.75% (peak area versus ng)), and detection limits (ng level) was validated and found to be satisfactory. The method was found to be reproducible and convenient for quantitative analysis of ceftriaxone, cefixime and cefotaxime in their raw materials and their dosage forms.

Cefotaxime was derivatised with 1,2-naphthoquinone-4-sulphonate (NQS), extracted into solid-phase cartridges (C18) and detected using a UV-visible detection system. Optimum conditions for this new procedure were: hydrogencarbonate-carbonate buffer, pH 10.5, 5-min reaction time at 25 degrees C and an NQS concentration of 7.1x10(-3) mol l(-1). The accuracy and the precision of the liquid-solid procedure were tested. The procedure was used to measure cefotaxime in pharmaceutical and urine samples. The results obtained were contrasted with those reported for a HPLC method for urine samples. The generalized H-point standard additions method was used to measure cefotaxime in urine samples.

Cefotaxime, given intravenously, is currently used as a broad-spectrum antibiotic for prophylaxis of intra- and postoperative infections in ocular lens surgery. A proposed therapeutic and economic alternative is the use of orally active fluoroquinolone ofloxacine as prophylactic agent. A HPLC method was developed for determination of both antibiotics in ocular aqueous humor and plasma in order to optimize dosage for safe surpassing minimal inhibitory concentration in the humor compartment. For plasma determinations a solid-phase extraction procedure was used with ciprofloxacine as internal standard. Detection limits for direct HPLC-analysis of ocular aqueous humor was 0.08 microg/ml for all compounds, whereas in plasma 0.31 microg/ml could be determined after solid-phase extraction.

Quantitative aspects of capillary zone electrophoresis (CZE) and micellar electrokinetic capillary chromatography (MECC) were investigated for the determination of cefotaxime (C) and its deacetyl metabolite (DA) in human plasma in a concentration range of therapeutic interest. For CZE, plasma samples spiked with C and DA were injected after deproteinization with acetonitrile, and analytes were separated in a fused silica capillary using a borate buffer at pH 9.2 as electrolyte; no suitable internal standard was found. For MECC, plasma samples spiked with C, DA, and theobromine as internal standard were directly injected after dilution with water and analyzed using a phosphate buffer, pH 8.00, containing 165 mM SDS as separation electrolyte and a fused silica capillary. Both methods gave satisfactory interday precision with respect to migration times (RSD < 1%) and gave linear responses over the concentration ranges investigated (5-100 mg L-1 C and 5-20 mg L-1 DA). For CZE, intraday RSD (n = 4 graphs) between the slopes of the calibration graphs was acceptable (5.7%) for C. The corresponding figures for interday precision (n = 4 days) were fair (16.1%) in comparison to those obtained with MECC, for which the RSD was 1.49% when theobromine was used as internal standard. A satisfactory interday precision between slopes was also obtained with MECC even without the use of an internal standard (RSD = 4.38%), which demonstrated the ruggedness of this method. Detection limits (S/N = 3) were about 2 mg L-1 (CZE) and 1 mg L-1 in plasma (MECC) for C and DA. MECC was shown to be superior with regard to simplicity, rapidity, precision, and sensitivity.

Background: The ability of an antibiotic to reach bactericidal concentrations in tissue depends on numerous factors including tissue composition and regional perfusion. Although necrotising pancreatitis is characterised by progression of pancreatic necrosis over at least 96 hours and microcirculatory alterations, the impact of these changes on the concentration of antibiotics in the pancreas has not yet been investigated., Aim: To determine and compare pancreatic tissue concentrations of imipenem and cefotaxime at different stages of acute necrotising pancreatitis in an animal model that has been shown to mimic closely the pathomorphological and bacteriological features of severe human pancreatitis., Method: Acute necrotising pancreatitis was induced in rats by a standardised intraductal infusion of glycodeoxycholic acid and intravenous cerulein. Six hours (n = 16) and 48 hours (n = 16) after induction of pancreatitis, the animals were randomised for intravenous therapy with either imipenem or cefotaxime. Fifteen minutes after injection of the antibiotic, the animals were killed. Blood and the head of the pancreas were collected for determining imipenem or cefotaxime in serum and tissue; the splenic portion of the pancreas was prepared for histological examination. In an additional set of identically treated animals, pancreatic capillary blood flow (PCBF) was assessed by intravital microscopy before induction of acute necrotising pancreatitis and at the time of antibiotic therapy., Results: Imipenem accumulates in the pancreas in the initial phase of acute necrotising pancreatitis characterised by pronounced oedema and decreased PCBF, and tends to decrease with resolution of the oedema and the progression of acinar cell necrosis in the later course of the disease. Concentrations of cefotaxime are low in oedematous pancreatic tissue early after induction of acute necrotising pancreatitis and increase with the resolution of oedema and normalisation of PCBF., Conclusions: Concentrations of antibiotics in the pancreas vary in acute necrotising pancreatitis, depending on changes in pancreatic tissue morphology and capillary blood flow. This suggests that antibiotic tissue concentrations may not be consistent from one agent to another and that efficacy of antibiotics in acute pancreatitis cannot be estimated solely on the basis of their pharmacological and microbiological properties.

Cephalosporins have structures and antibiotic activity similar to those of penicillins which represent a class of compounds with closely related structures. Most of the cephalosporins contain aromatic groups and show distinctive UV spectra. Separating the different types of cephalosporins is a challenging task for HPLC. but the resolving power of capillary zone electrophoresis (CZE) makes this separation fast and simple. The present study reports the application of CZE for cephalosporin analysis and the separation of cephalosporins from plasma. Both field strength and temperature were shown to influence the plate number. The influence of injection time on the peak height was studied. Furthermore, the influence of pH value on the separation of cephalosporins by CZE was investigated. The low sample amount required and the relatively short analysis time are the main advantages of this method.

The penetration of oral cefixime into the synovial fluids of 16 patients (mean age, 50.6 years) who underwent joint taps for rheumatic noninfectious disorders was examined. The patients were each given a single dose (400 mg) 2 to 24 h prior to the tap. Cefixime concentrations in serum and joint fluid samples were measured by high-performance liquid chromatography, and the bactericidal activities of these fluids against three isolates each of Haemophilus influenzae and Escherichia coli were examined. The highest concentrations in serum and synovial fluid were achieved 4 h following drug intake, the mean values being 2.8 and 2.03 micrograms/ml, respectively. Effective bactericidal activities (bactericidal titer, > 1:2) against E. coli and H. influenzae were demonstrated in serum and joint fluid up to 10 h following oral intake of cefixime. These results suggest that cefixime penetrates well into joint fluid, achieving levels above the MIC for E. coli lasting as long as 10 h and levels above the MIC for H. influenzae lasting up to 24 h after administration. Good bactericidal activity against susceptible bacterial isolates was observed for at least 10 h after dosing.

A sensitive, accurate, precise and the same time simple and rapid method for the colorimetric determination of some cephalosporins of the second and third generations, such as: cefoxitin sodium (CFXT), cefaclor (CFCL), cefamandole nafate (CFMD), ceforanide l-lysine (CFRN), cefotaxime sodium (CFTX), and cefurozime sodium (CFRX) was described. The new method proposed is based: a) On the reduction of Fe(III) to Fe(II) by the drug analysed and b) On complexation of Fe(II) formed with o-Phenanthroline (O-Phen) consistently the formation of the well known highly stable orange-red coloured chelate complex [Fe(II)-(o-Phen)3]2+ which exhibits an absorption maximum at lambda = 510 nm (pH 4.50 +/- 0.2). Beer's law is obeyed for: 1.0 - 37.5 microgram mL-1 for CFX, 1.0 - 25.0 microgram mL-1 for CFMD, CFRN, and CFTX and 2.0 - 37.5 microgram mL-1 for CFTX and CFCL, while the apparent molar absorptivity ( epsilon in L mol-1cm-1) and the Sandell's sensitivity in (ngcm-2) both referred to the drug analyzed, are 1.29 x 10(4); 34.7 (CFXT), 7.61 x 10(3); 50.7 (CFCL), 3.33 x 10(4); 15.4 (CFMD), 2.60 x 10(4); 17.6 (CFRN) respectively. The regression line equation for each one of the above studied cephalosporins were calculated with a correlation coefficient 0.9997 < r < 1.0000; the accuracy and the precision of the method was considered as very satisfactory, while the results of a statistical analysis by means of the Student's t-test and the variance ratio F-test prove that no significant difference was observed between the results of the proposed method and those of official one.

Ro 23-9424 is a broad-spectrum antibacterial agent consisting of a cephalosporin and a quinolone moiety which are held together by an ester linkage. This compound has limited solubility in water but is more soluble at alkaline pH. Such high pH values, however, lead to stability problems due to the lability of the ester linkage, and result in the formation of the free quinolone and cephalosporin moieties. The balance between solubility and stability presents a challenge in formulation development for this compound. Thus, it is important to effectively monitor the stability of Ro 23-9424 after it has been reconstituted in different solvent systems. In this manner, a diluent which does not lead to degradation of the drug can be identified. A capillary electrophoresis method was developed and validated to monitor the stability of Ro 23-9424. The method was found to meet acceptable criteria for method precision, system precision, linearity and limits of detection and quantitation. The method was used to monitor the stability and measure the half-life of Ro 23-9424 in water and in an L-arginine-sodium benzoate-saline diluent designed to mimic the drug delivery system. This work shows that capillary electrophoresis can be used to compare the stability of a drug in different solutions as an aid in formulation development.

Cefotaxime sodium (CAS 64485-93-4) is a semisynthetic cephalosporin derivative belonging to the third-generation cephalosporins. Owing to its broad antibacterial activity and its high resistance to beta-lactamases it can be used for a large variety of infections. In the present study the quality standard of 15 different cefotaxime sodium manufacturers from 9 different countries has been examined. The best results were received for the preparation Claforan. None of the 14 other products showed comparable results especially with respect to particulate matter and by-products. The particulate contamination of the 14 foreign products showed relatively high values although they still comply with the limits set by the pharmacopoeias. In contrast, in Claforan very few particles were found in the solution. This is of importance as the drug has to be administered either i.v. as an infusion or i.m. as an injection. Also the amount of by-products measured in the 14 foreign preparations was about 1.5 times higher than the one measured for Claforan. Although these are not critical results, they do indicate that there are marked differences between the quality of the products from different countries which should be taken into account.

Increasing use of medicinal leeches has been accompanied by increasing numbers of reports of Aeromonas hydrophila infections after leech application on or near damaged tissue. We examined the enteric contents of postprandial leeches after their application to patients receiving antibiotics. We found measurable levels of antibiotic in the leech enteric contents, and in leeches applied to patients receiving an antibiotic effective against Aeromonas hydrophila, there was a significant decrease in positive Aeromonas enteric cultures. Suppression of leech enteric bacteria by antibiotic administration to the patient may be an effective strategy to prevent invasive infection by Aeromonas hydrophila as well as bacterial colonization of devitalized tissue that could be the source of late infection. Clinical studies will be required to clarify whether suppression of leech enteric flora results in a decrease in infections associated with leech use.

The penetration of Cefixime (CFIX) into the prostatic tissue and the serum was examined in 54 patients with benign prostatic hypertrophy treated with transurethral resection of the prostate. CFIX was administered orally in a dose of 200 mg 2 times daily for 3 days preoperatively. The blood samples were taken at the time of the tissue sampling. The patients were divided into 2 groups. In group 1 (16 patients), the tissue sampling was done about 17 hours after the final drug administration. The mean concentration of CFIX was 0.83 +/- 0.49 micrograms/g in the prostatic tissue and 0.84 +/- 0.63 micrograms/ml in the serum. In the prostatic tissue, CFIX was detected in only 4 patients, in the other 12 patients, CFIX was not detected. In group 2 (38 patients), tissue sampling was done 5.5 hours after the final drug administration. The mean concentration of CFIX was 1.08 +/- 0.47 micrograms/g in the prostatic tissue and 3.18 +/- 1.28 micrograms/ml in the serum.

Cefixime is a new orally active third-generation cephalosporin with a broad spectrum of activity against a variety of both gram-positive and -negative bacteria including many beta-lactamase-producing strains of streptococci, Haemophilus influenzae, Neisseria gonorrhoeae, and the majority of the Enterobacteriaceae. Activity of cefixime against Staphylococcus aureus, enterococci, Listeria monocytogenes, and Pseudomonas spp. is poor. The relatively long elimination half-life of cefixime (approximately 3.0 h) has made possible once- to twice-daily administration with the potential added benefit of improved patient compliance. Clinical trials indicate that cefixime is at least as effective as standard agents in the treatment of genitourinary and upper respiratory tract infections. The incidence of resistant organisms reported during clinical trials with cefixime was low. Adverse reactions observed during clinical trials were relatively uncommon and generally mild and transient in nature. The most significant adverse reactions reported were diarrhea and stool changes occurring in up to 20 percent of patients.

In a study of 58 patients the concentrations of cefixime, a new oral cephem antibiotic, in bronchial mucosa were 35-40% of the concentrations found in simultaneously collected serum samples. The antibiotic was often undetectable in sputum despite a highly sensitive assay.

The stability of cefotaxime sodium at room and body temperatures in peritoneal dialysis solutions containing 1.5% or 4.25% dextrose was determined. Cefotaxime sodium 2 g was added to three 2-L bags of dialysis solution containing 1.5% dextrose, and cefotaxime sodium 500 mg was added to three 500-mL bags of dialysis solution containing 4.25% dextrose. The bags were stored at 25 or 37 degrees C Samples from bags stored at 25 degrees C were drawn aseptically at 0, 12, 24, 48, and 72 hours, and samples from bags stored at 37 degrees C were drawn at 0, 6, 12, and 24 hours. The pH of each sample was determined, and the cefotaxime concentration was measured by a stability-indicating high-performance liquid chromatographic method. At 37 degrees C the initial mean cefotaxime concentration declined to 97.9% at six hours, 89.1% at 12 hours, and 68.8% at 24 hours in the 1.5% dextrose solution; the mean percentages remaining in the solution containing 4.25% dextrose were 96.4%, 86.1%, and 71.0% at 6, 12, and 24 hours, respectively. At 25 degrees C the initial cefotaxime concentration declined to 92.4%, 84.4%, and 74.2% at 24, 48, and 72 hours, respectively, in 1.5% dextrose solution and to 92.0%, 84.3%, and 80.3% at 24, 48, and 72 hours, respectively, in 4.25% dextrose solution. In both solutions, cefotaxime concentration decreased by more than 10% at and after 12 hours at 37 degrees C and between 24 and 48 hours at 25 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

In a prospective study, 50 women patients were given 2 g Ceftriaxon (Rocephin) as a short infusion before performing hysterectomy. A control group of 50 patients remained without any antibiotic treatment. In 31 patients, the concentration of Ceftriaxon in the serum and tissue was determined at the time the uterus was removed. Due to the long half-life of Ceftriaxon (8 hours), high serum and tissue levels were found for a period of many hours. After 4-5 hours, the serum level was still 100 micrograms/ml, whereas the concentration in the endometrium, myometrium and in the salpinges were 21 micrograms/g, 24 micrograms/g and 31 micrograms/g, respectively. Due to these long-lasting serum and tissue levels, the protective effect against infections was also very high. 15 infections in the control group are contrasted by one infection only in the treated group. The efficacy of the prophylaxis is objectively assessed by measuring the temperature curve and by determining the number and the spectrum of the postoperatively isolated germs. The germs isolated in the treated group are exclusively such germs which are resistant to Ceftriaxon (enterococci) or which are only moderately sensitive to Ceftriaxon, such as Bacteroides.