Determination of cefotaxime, cefoperazone, ceftazidime and cefadroxil using surface plasmon resonance band of silver nanoparticles

The aim of this work is to evaluate simple, sensitive, effective and validated procedures for the determination of cefotaxime, cefoperazone, ceftazidime and cefadroxil. In this study, the methods based on the ability of the cited drugs to reduce Ag+ ions to silver nanoparticles (Ag-NPs) in the presence of Polyvinyl Pyrrolidone (PVP) as a stabilizing agent producing very intense surface plasmon resonance peak of Ag-NPs (λmax. = 410-430 nm). The plasmon absorbance of the Ag-NPs allows the quantitative spectrophotometric determination of the cited drugs. The calibration curves are linear with concentration ranges of 0.4-3.2, 1-8, 0.5-4.0 and 1.5-9.0 µg/mL for cefotaxime, cefoperazone, ceftazidime and cefadroxil, respectively. Apparent molar absorptivity, detection and quantitative limits are calculated. Applications of the proposed methods to representative pharmaceutical formulations are successfully presented. The extracellular synthesis of nanoparticles is fast, and the method doesn't require various elaborate treatments and tedious extraction procedures.

Application of acetone acetals as water scavengers and derivatization agents prior to the gas chromatographic analysis of polar residual solvents in aqueous samples.

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.

Simultaneous quantification of cefotaxime, desacetylcefotaxime, ofloxacine and ciprofloxacine in ocular aqueous humor and in plasma by high-performance liquid chromatography.

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.

Postprandial Aeromonas hydrophila cultures and antibiotic levels of enteric aspirates from medicinal leeches applied to patients receiving antibiotics.

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.

[Cefixime concentration in human prostatic tissue following 3-days of administration].

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.

[Cefotaxime levels in synovial fluid following intravenous administration]. / Cefotaxim-Konzentrationen in der Gelenkflüssigkeit nach intravenöser Gabe.

The corresponding levels of cefotaxime in serum and synovial fluid were investigated in patients undergoing surgery under perioperative antibiotic medication. By investigating 32 samples a concentration band over 4 hours could be established. Clinically relevant levels of the drug could be found from 10 minutes after start of the intravenous dose with an increase up to 30 minutes. Between 30 and 90 minutes the average concentration was about 40 micrograms/ml. After 90 minutes a decrease of the concentration was found and the median lines for synovial and serum concentrations crossed at about 105 minutes. Even after 4 hours we found synovial titers of 10 to 20 micrograms/ml having therapeutical relevance. From the results we can conclude, that cefotaxime infusion of 2 g produced over hours therapeutical synovial levels being significantly over the break point of 16 micrograms/ml for bacteria susceptible to this antibiotic agent. On the other hand we strongly recommend not to wait too long with surgical intervention when a joint infection does not improve significantly in 48 hours under systemic antibiotic treatment.

Ceftizoxime level in the myocardium (right atrial muscle and mitral papillary muscle) during open heart surgery.

We determined the level of sodium ceftizoxime (CZX) in the right atrium and mitral papillary muscle of 22 adults and 6 children undergoing open-heart surgery, 60 and 120 minutes after intravenous administration of this drug at the dosages of 2 grams for adults and 1 gram for children. The CZX level in the right atrial muscle after 60 minutes was 37.0 micrograms/g in adults and 51.0 micrograms/g in children. The CZX level in the papillary muscle of the mitral valve, determined at 120 minutes was 16.9 micrograms/g. In the present study, we measured the level of the antibiotic CZX in the myocardial tissue during open-heart surgery. The purpose of this was to determine the quantity in which the antibiotic is taken into the myocardial tissue.

Serum and tissue concentrations of cefoxitin and cefotaxime in women undergoing hysterectomy.

In a comparative study of serum and uterine tissue concentrations of cefoxitin and cefotaxime in patients undergoing hysterectomy, 40 patients were randomised to receive either cefoxitin 2g or cefotaxime 2g by intravenous administration. Serum samples were obtained before drug administration, at the ligation of the uterine arteries and at the end of surgery. Cefoxitin, cefotaxime and desacetylcefotaxime concentrations were determined by high performance liquid chromatography. The composite serum half-lives (determined by linear regression) for cefoxitin, cefotaxime and desacetylcefotaxime were 0.8, 0.7 and 2.1 hours, respectively. Although serum concentrations were higher for cefotaxime than for cefoxitin after a 2g dose, the uterine concentrations (at 40 mins) of cefoxitin were higher (51 micrograms/g vs 16 micrograms/g) than those of cefotaxime. After a 2g dose of cefotaxime the desacetylcefotaxime peak uterine concentration was 8 micrograms/g. Both drugs achieved adequate concentrations in serum and uterine tissue to prevent and treat infections caused by common Enterobacteriaceae such as Escherichia coli, with cefotaxime having a longer apparent duration of activity. However, cefoxitin provided serum and uterine concentrations above the minimum inhibitory concentration of Bacteroides fragilis for a longer period than did cefotaxime.

Concentrations of cefmenoxime in human tissues.

Concentration levels of cefmenoxime were studied in human bone, muscle, fascia, cerebrospinal fluid, and synovial fluid. Tissue samples were taken 30 to 50 minutes after intravenous injection of 2,000 mg of cefmenoxime just before operation in patients undergoing orthopedic surgery. Levels were compared with those in the blood serum of the same patients. Cefmenoxime levels were also compared with levels of other cephalosporins examined by the same techniques and, with one exception, were found to be higher than those produced by the other agents. Cefmenoxime does not produce undesirable side effects, as do the other cephalosporins. Assay techniques for various tissues are described.

[Concentrations of cefotaxime in serum and myocardial tissue].

Serum and myocardial concentrations of cefotaxime (CTX) were measured in 20 adult patients undergoing cardiac surgery. To all of these patients 1.0 g of CTX was given intravenously (in the range of 13.7--29.0 mg/kg) at the beginning of operation. The serum concentrations of CTX were determined at 5, 10, 30, 60 minutes and 120 minutes after administration. Myocardial concentrations of CTX were also determined at about 30 minutes (group I), 60 minutes (group II) and 120 minutes (group III). The following results were obtained. Average serum CTX concentrations were 132.8 +/- 34.1 micrograms/ml at 5 minutes, 92.0 +/- 23.1 micrograms/ml at 10 minutes, 44.6 +/- 12.3 micrograms/ml at 30 minutes, 24.5 +/- 7.7 micrograms/ml at 60 minutes and 12.3 +/- 4.9 micrograms/ml at 120 minutes after administration. Average myocardial CTX concentrations were 10.0 +/- 3.7 micrograms/g in group I, 3.6 +/- 2.1 micrograms/g in group II and 2.3 +/- 1.8 micrograms/g in group III. The myocardial/serum concentration ratio was 0.22 +/- 0.14 in group I, 0.15 +/- 0.08 in group II and 0.18 +/- 0.12 in group III, respectively. These results suggested that the serum and myocardial concentrations of CTX were high enough to be prophylactic and therapeutic against not only aerobic but also anaerobic and opportunistic infections during and after cardiac surgery.

[Antibiotic prevention in gynecology. Concentrations of ceftizoxime in the serum, myometrium, endometrium and fallopian tubes]. / Antibiotikaprophylaxe in der Gynäkologie. Konzentrationen von Ceftizoxim in Serum, Myometrium, Endometrium und Tuben.

34 patients received an intravenous bolus injection of 2 g ceftizoxime over 5 min at various times before abdominal or vaginal hysterectomy. Ceftizoxime concentrations in myometrium were substantially higher than in salpinges and endometrium. Tissue concentrations of 4 micrograms/g could be maintained for at least 3 hours. The ceftizoxime tissue concentrations attained in myometrium, endometrium and salpinges justify therapeutic studies and controlled prospective clinical trials on the prevention of postoperative wound infections with this antibiotic.

[Antibiotic prevention in hysterectomy. Effectivity of a single preoperative ceftriaxon dose]. / Antibiotika-Prophylaxe bei Hysterektomie. Studie über die Wirksamkeit der einmaligen präoperativen Gabe von Ceftriaxon (Rocephin).

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.

[Cefotaxim for peri-operative short-term prophylaxis of infection in cardiac surgery. Concentrations in myocardial, pericardial, fat and skeletal muscle tissues]. / Cefotaxim zur perioperativen Kurzzeitprophylaxe bei herzchirurgischen Eingriffen. Konzentrationen im Herzmuskel-, Perikard-, Fett- und Skelettmuskel-Gewebe.

Cefotaxim was administered intravenously in a dose of 50 mg/kg body-weight before and immediately after cardiac surgery. The drug's concentrations were measured in serum, myocardium, peri-operative fat, pericardium and skeletal muscle. The highest concentration was found 15 minutes after injection: 32 micrograms/g in pericardium, 22 micrograms/g in myocardium, 17.9 micrograms/g in fat and 12.3 micrograms/g in skeletal muscle. After 2 hours the average concentration in pericardium was 10.7, in myocardium 3.8, in fat 5.4 and in skeletal muscle 2.4 micrograms/g. The corresponding mean serum levels were 237.4 and 33.3 micrograms/ml, respectively. The tissue concentrations were thus high enough to be effective against infections caused by cefotaxim-sensitive organisms. There was primary wound healing in all 16 patients. No other infections, such as pneumonia or urinary infections, occurred.