Determination of cephalosporins in solid binary mixtures by polarized IR- and Raman spectroscopy.

Quantitative IR- and Raman spectroscopic determinations of four cephalosporin antibiotics in six solid binary mixtures have been conducted. This is a new approach for spectroscopic determination of these antibiotics, since the corresponding quantitative analysis in solution only has been reported so far. The correlation coefficient r2 was found to be in the confidence intervals within 99.32-99.88% and 99.90-95.54% for the systems under study by using the absorption ratios of the characteristic bands at 800 cm(-1) and 721 cm(-1) present in the IR- and Raman spectra of the antibiotic compounds cephalexin, cephalotin, cephaloglycin and cephamandole, respectively. Solid-state linear dichroic infrared (IR-LD) spectral analysis of the solid mixtures was carried out in order to obtain experimental IR-spectroscopic assignment of the compounds studied. Independent high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis was performed for the validation of the vibrational spectroscopic data. The application of this instrumental analytical tool for the analysis of 10 tablets of the commercial products Cefamandole and Cefalotin (Actavis) was also studied.

Analytical investigation of beta-lactam antibiotics in pharmaceutical preparations. IX. Colorimetric determination of six cephalosporins of second and third generation in the range of micromolar concentrations.

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.

Timing of antibiotic administration in knee replacement under tourniquet.

Cephamandole levels in serum and drain fluid were measured in 32 knee replacement operations to determine the benefit of an intravenous dose of antibiotic at the time of tourniquet deflation. Concentrations of cephamandole in drain fluid were directly proportional to the serum concentration at the time of tourniquet release. A 'tourniquet-release' dose of antibiotic increased drain fluid concentration threefold.

Determination of bone and fat concentrations following systemic cefamandole and regional cefuroxime administration in patients undergoing knee arthroplasty.

Five patients undergoing routine total knee replacement received standard antibiotic prophylaxis of 1000 mg of iv cefamandole and also regional administration of 750 mg of cefuroxime. Regional dosing was carried out at the start of the operation, following the application of a mid-thigh tourniquet, by administration into a foot vein. Samples of bone and fat were collected during the operation and assayed for cefuroxime and cefamandole by HPLC analysis. The mean cefuroxime bone (133.1 mg/l) and fat (88.4 mg/l) levels following regional administration were significantly higher (P less than 0.001) than the mean cefamandole bone (9.1 mg/l) and fat (9.8 mg/l) levels following systemic dosing. The possibility of administration of prophylaxis by the regional route is suggested.

Simultaneous determination of cefamandole and cefamandole nafate in human plasma and urine by high-performance liquid chromatography with column switching.

A high-performance liquid chromatographic method with column switching has been developed for the simultaneous determination of cefamandole and cefamandole nafate in plasma and urine. The plasma and urine samples were injected onto a precolumn packed with Corasil RP C18 (37-50 microns) after simple dilution with an internal standard solution in 0.05 M phosphoric acid. Polar plasma and urine components were washed out using 0.05 M phosphoric acid. After valve switching, the concentrated drugs were desorbed in back-flush mode and separated by a reversed-phase C8 column with methanol-5 mM tetrabutylammonium bromide (45:55, v/v) as the mobile phase. The method showed excellent precision with good sensitivity and speed, and a detection limit of 0.5 microgram/ml. The total analysis time per sample was less than 30 min, and the mean coefficients of variation for intra- and inter-assay were both less than 4.9%. The method has been successfully applied to plasma and urine samples for human volunteers after intravenous injection of cefamandole nafate.

[A pharmacokinetic study of diffusion in adenomatous prostatic tissue of an intravenous bolus of cefamandole]. / Etude pharmacocinétique de la diffusion dans le tissu prostatique adénomateux d'un bolus intra-veineux de céfamandole.

Twenty-three patients undergoing transurethral resection of the prostate for benign prostatic hypertrophy received antibiotic prophylaxis with a second generation cephalosporin, cefamandole, administered by a single IV bolus of 2.5 g. A pharmacokinetic study was performed on blood and resection chips collected at regular intervals. Cefamandole penetrates rapidly into the prostate without any saturation threshold. It diffuses less extensively and persists for a shorter period in elderly subjects, but penetrates to an identical degree regardless of the volume of the adenoma. The prostatic concentration was always higher than the minimal inhibitory concentration for the bacteria generally encountered, except for pseudomonas. The pharmacokinetic study of cefamandole therefore demonstrated that an IV bolus of 2.5 g is perfectly suitable for antibiotic prophylaxis prior to prostatic resection.

Spectrophotometric determination of certain cephalosporins using molybdophosphoric acid. Part II. Determination of cefadroxil, cefapirin, ceforanide and cefuroxime.

The use of molybdophosphoric acid as an oxidising agent for the spectrophotometric determination of four cephalosporin derivatives, viz., cefadroxil monohydrate (I), cefapirin sodium (II), ceforanide L-lysine (III) and cefuroxime sodium (IV), either in the pure form or in pharmaceutical formulations is described. Beer's law is obeyed up to 100 micrograms ml-1 for I, up to 60 micrograms ml-1 for II and IV and up to 80 micrograms ml-1 for III. The molar absorptivities were 4.58 X 10(3), 11.3 X 10(3), 9.8 X 10(3) and 10.9 X 10(3) l mol-1 cm-1 and the Sandell sensitivities were 83.3, 39.3, 53.0 and 41.0 ng cm-2 for I, II, III and IV, respectively. The slopes and intercepts of the equations of the regression line were calculated for each of these drugs with the following correlation coefficients: I, 0.9993; II, 0.9999; III, 1.000; and IV, 0.9999. These antibiotics were determined successfully both in the pure form and in pharmaceutical preparations. The results demonstrated that the proposed procedure is at least as accurate, precise and reproducible as the official methods, while being simpler and less time consuming. A statistical analysis indicated that there was no significant difference between the results obtained by the proposed procedure and those of the official methods.

Centrifugation of antibiotic impregnated bone cement.

Centrifugation is used to increase the strength of bone cement in total joint arthroplasty. Antibiotics have been incorporated into cement for the treatment and prophylaxis of infection. To determine the effect of centrifugation on antibiotic containing cement, tobramycin and cefamandole impregnated Surgical Simplex P polymethylmethacrylate was centrifuged using manufacturers' techniques. The concentration of antibiotics was measured throughout the cement column by a zone of inhibition bioassay. No difference in the distribution of the antibiotics could be demonstrated as compared to hand mixed controls. Centrifugation decreased the number of large air inclusions overall, however, a significant number were noted to remain at the top of the centrifugation gradient. It was concluded that centrifugation of an antibiotic impregnated bone cement, utilizing this technique, may be used without disturbing the antibiotic distribution. Discarding the top 1 cm of liquid centrifuged column to remove residual air inclusions is recommended.

A note on the effect of gamma-rays on cefamandole and oxacillin.

The feasibility of the radiation sterilization of two beta-lactam antibiotic powders, cefamandole nafate and oxacillin sodium, has been examined by subjecting them to a range gamma-radiation doses, followed by chemical and microbiological analyses. It would appear feasible to radiation sterilize oxacillin sodium. The radiation sterilization of cefamandole nafate may be realistic at low doses or under conditions that minimize radiolysis.

Antibiotic prophylaxis in vascular surgery: pharmacokinetic study of four commonly used cephalosporins.

Plasma levels of antibiotics often do not correlate well with their tissue levels. To determine optimal antibiotic coverage for prophylactic effect in vascular surgery, we studied the tissue pharmacokinetics of four cephalosporins in dogs: cefazolin, cefoxitin, cefamandole, and moxalactam for 3 hours after a single (25 mg/kg) intravenous injection. The minimal inhibitory concentration (MIC) of these antibiotics for the three most common pathogens involved in graft infections (Staphylococcus aureus, S. albus, and Escherichia coli) and their tissue concentration (TC) in the plasma, muscle, subcutaneous tissue, and aortic wall were assayed. The data are presented as TC/MIC ratio. Cefoxitin and moxalactam failed to achieve an effective therapeutic TC/MIC ratio (greater than 10) for S. aureus and S. albus in all the tissues studied whereas cefoxitin and cefamandole were above therapeutic levels. All antibiotics achieved an effective therapeutic ratio against E. coli, but cefamandole performed better (p less than 0.05) than cefoxitin; the latter reached effective levels at 3 hours. Cefamandole attained the most effective bioactive aortic tissue levels when the three most common pathogens were considered together and should therefore be considered as an antibiotic agent of choice for prophylaxis in vascular surgery.

Liquid-chromatographic assay of cefamandole in serum, urine, and dialysis fluid.

We describe a "high-performance" liquid-chromatographic assay for quantifying cefamandole in biological fluids from patients with renal impairment. Serum samples are deproteinized with acetonitrile, then extracted with dichloromethane; dialysis-fluid samples are injected directly; urine samples are diluted appropriately before injection onto the reversed-phase column. The mobile phase is a methanol/aqueous solution (31/69 by vol) containing 500 microL of phosphoric acid, 20 mmol of sodium sulfate, and 200 microL of triethylamine per liter, the mixture being adjusted to pH 6.0 with NaOH. Retention time for cefamandole is 12 min. Its peak is well resolved in highly contaminated samples from renally impaired subjects. The assay's selectivity, reproducibility (within-day and between-day CVs less than 8% in all three sample fluids), and sensitivity--0.5 mg/L in serum, 1.0 mg/L in dialysis fluid, and 5.0 mg/L in urine--make it applicable to pharmacokinetic studies.

Chemical stabilities of cefamandole nafate and metronidazole when mixed together for intravenous infusion.

The chemical stabilities of cefamandole nafate and metronidazole, when mixed together for intravenous infusion, have been studied using a stability-indicating, high-performance liquid chromatographic method of assay. Cefamandole nafate was stable for 5 days at 25 degrees C and at least 14 days at 5 degrees C. The addition of metronidazole did not affect the stability of cefamandole nafate. In a 2% solution of cefamandole in metronidazole injection (0.5%), metronidazole lost about 9.1% of potency in less than 2 h at 25 degrees C and in less than 6 h at 5 degrees C. The per cent loss was directly related to the initial concentration of cefamandole nafate. Change in the concentration of metronidazole did not affect the per cent of metronidazole lost.

Stability of clindamycin phosphate and ceftizoxime sodium, cefoxitin sodium, cefamandole nafate, or cefazolin sodium in two intravenous solutions.

The stability and compatibility of clindamycin phosphate and ceftizoxime sodium, cefoxitin sodium, cefamandole nafate, or cefazolin sodium in two intravenous solutions were studied. Each antibiotic alone as well as each of the four two-drug combinations were examined when mixed in duplicate 100-mL glass bottles of 5% dextrose and 0.9% sodium chloride injections. Antibiotic concentration, pH, and visual appearance were recorded at the time of preparation and at 1, 4, 8, 12, 24, and 48 hours. Antibiotic concentrations were assessed with drug-specific high-performance liquid chromatographic assays. Decreases in concentration of 10% or more from the original concentration were considered to indicate instability. All the single antibiotic solutions were stable for 48 hours. Clindamycin was stable in all combinations except with ceftizoxime in 0.9% sodium chloride injection, which measured 89.3% of its original clindamycin concentration at 48 hours. All the cephalosporins mixed with clindamycin were stable for 48 hours. Clindamycin is stable for at least 48 hours when mixed with cefoxitin sodium, cefamandole nafate, or cefazolin sodium in either 5% dextrose or 0.9% sodium chloride injections and for at least 24 hours when mixed with ceftizoxime sodium in 0.9% sodium chloride injection.

Cefamandole levels in serum and necrotic bone.

Seven patients with chronic osteomyelitis were treated by surgical debridement. Cefamandole was administered intravenously before surgery. During the debridement, cefamandole concentrations were measured in serum and necrotic bone. Although adequate levels of antibiotic were achieved in the serum, minimal or no concentration of antibiotic was found in the necrotic bone. There was only minimal penetration of cefamandole into necrotic bone.

Stability of cefonicid sodium in infusion fluids.

The chemical stability of cefonicid sodium in infusion fluids was analyzed. Cefonicid sodium vials were reconstituted and diluted with sterile water for injection and other commonly used intravenous fluids to concentrations of 325, 220, 40, 20, and 5 mg/mL. Cefonicid concentration was analyzed by high-performance liquid chromatography initially and after storage at room temperature and 5 degrees C. Reconstituted vials were frozen as long as eight weeks, thawed, and kept at room temperature and 5 degrees C and then analyzed. Cefonicid sodium reconstituted in each of the diluents studied exhibited no change in clarity and very little change in potency after 24 hours at room temperature and after 72 hours at 5 degrees C. Some vials with high concentrations became turbid between 72 and 96 hours at 5 degrees C. The thawed vials were chemically stable for 24 hours at room temperature and for 96 hours at 5 degrees C. When reconstituted with sterile water for injection and other commonly used intravenous fluids, cefonicid sodium vials and small-volume infusions are chemically stable for 24 hours at room temperature and for 72 hours at 5 degrees C. Reconstituted cefonicid sodium vials can be frozen and stored for as long as eight weeks, thawed, and then kept at room temperature for 24 hours or at 5 degrees C for 72 hours.

High-performance liquid chromatographic determination of cefonicid in human plasma and urine.

A high-performance liquid chromatographic assay for determination of cefonicid concentrations in human plasma and urine samples has been developed using cefazolin as an internal standard. For the analysis of plasma samples two calibration curves were utilized covering the cefonicid concentration ranges of 0.05-1.0 microgram/ml and 1.0-50.0 micrograms/ml, respectively. Coefficients of variation of 7.4% or less were obtained for cefonicid concentrations of 0.05-50.0 micrograms/ml. Mean bias was +6.0% at 0.05 micrograms/ml cefonicid and between -2.1% and +1.6% for 1.0-50.0 micrograms/ml cefonicid. Plasma samples containing 30 ng/ml cefonicid could be well distinguished from blank plasma samples. Urine samples were analysed by using a calibration curve for cefonicid concentrations between 1.0 and 50.0 micrograms/ml. ranged from 8.6% at a cefonicid concentration of 1.0 microgram/ml to 0.5% at 50.0 micrograms/ml with a mean bias between -3.0% and +0.3%.

Cefoxitin and cefamandole levels in the human bile.

The bile levels of cefoxitin and cefamandole were studied in 75 patients. The two antibiotics were shown to be present at high concentration and to undergo a rapid metabolization. It is concluded that they represent the antibiotics of choice in the prophylactic and therapeutic treatment of biliary tract infections.

Comparison of cefamandole and cefazolin during cardiopulmonary bypass.

In a randomized comparison, concentrations of cefazolin were found to exceed those of cefamandole in serum, atrial appendage, and sternal bone in patients undergoing cardiopulmonary bypass. No postoperative infections and no antibiotic-related complications occurred in either patient group.