茜素分光光度法测定磷霉素钠

在乙醇体系中,磷霉素钠与茜素发生反应,生成稳定的1∶1的络合物,溶液颜色发生明显改变,其最大吸收波长为545nm,磷霉素钠的浓度在1.4—60mg·L-1范围内遵守比耳定律,表观摩尔吸光系数ε=3.47×103L·mol-1.cm-1,基于以上反应,本方法测定药物制剂含量与文献方法一致,回收率在99.6%—100.5%之间,结果满意。     

The structure of fosfomycin salts in solution and in the solid state by nuclear magnetic resonance spectroscopy and DFT calculations

Two samples of fosfomycin salts, the calcium and the disodium ones, were used to record their NMR spectra both in solution and in the solid state. The existence of fosfomycin in a neutral and two ionized structures (mono and dianion) was considered to interpret the spectra that were solved using the GIAO calculated chemical shifts of the minimum energy conformations. Although the starting materials were dianions, the spectra in solution show the presence of monoanions.     

Development and validation of a gas chromatographic method for analysis of fosfomycin in chicken muscle samples

Summary A gas chromatographic method for the determination of residues of Fosfomycin in chicken muscle samples has been developed. Muscle samples were homogenised with TRIS buffer, containing phenylphosphonic acid (as internal standard) and Fosfomycin using a tissue homogenizer. Afterwards, the samples were ultrafiltered and the ultrafiltrate was evaporated to dryness. A silylation reagent for derivatization was used in order to reconstitute the residue. The linear concentration range of application was 10–150 μgg⁻¹, with a detection and quantitation limit of 3.11 and 10 μgg⁻¹, respectively. The method was efficient with a mean recovery of 87.83% from spiked muscle. The results obtained show that gas chromatography is a useful method for the determination of Fosfomycin residues in chicken muscle samples.     

Chromatographic analysis of some alkylphosphonic acids using a conductimetric detection. Application to fosfomycin determination

Summary This paper describes an ion chromatographic technique with conductimetric detection for the rapid quantitative analysis of alkylphosphonic acids. The choice of the mixture of acetonitrile/borategluconate buffer (1288 v/v) as the mobile phase is discussed: acetonitrile was added to decrease the retention time of phenylphosphonic acid and fosfomycin. Simultaneously the background conductivity was smaller. Borate/gluconate buffer showed the good buffer capacity at pH=8.5 required for the injection of strong acids. The pH was set at 8.5 to obtain the fully dissociated species since their monoionic forms are poorly retained. No eluent suppression process was necessary since the mobile phase led to a low background conductivity. The validation of the method has been studied. Linearity was determined over a concentration range of from 10 to 80 g·ml^–1. Intra- and inter-day reproducibilities were satisfactory with relative standard deviations respectively less than 1.0 and 4.8%. The lowest detectable limits were from 0.2 to 1.0 g depending on the analysed compound. The method has been successfully applied to the determination of fosfomycin in biological samples.     

Rapid analysis of alkylphosphonate drugs by capillary zone electrophoresis using indirect ultraviolet detection

A rapid capillary electrophoretic method for the analysis of three alkylphosphonate drugs (i.e. fosfomycin disodium (FOS), clodronate disodium (CLO) and alendronate sodium (ALN)) was developed by using multiple probe BGE and indirect UV detection. BGE containing 30 mM benzoic acid, 5 mM salicylic acid and 0.5 mM CTAB (pH 3.8), temperature of 30°C, applied voltage of ?30 kV and detection at 220 nm provided baseline separation of all analytes (resolution (R)>2.2) in 3.2 min. EOF reversal by addition of CTAB and negative voltage polarity leading to the co‐EOF flow and short analysis time. Two probe BGE greatly improved peak symmetry. The method showed good linearity (r²>0.999 in ranges of 20–1000 μg/mL for FOS, 100–1000 μg/mL for CLO and 100–750 μg/mL for ALN) repeatablitiy (RSD<2.15%), recovery (99.3–101.1%) and sensitivity (LOD<50 μg/mL). Freshly prepared BGE and sample solutions are essential for the method precision and accuracy. This new method can be utilized for routine analysis of FOS, CLO and ALN in dosage forms because of its efficiency, reliability, speed and simplicity.     

Determination of fosfomycin in human urine by capillary gas chromatography: Application to clinical pharmacokinetic studies

Summary A capillary gas chromatographic method for the determination of fosfomycin in human urine is described. After dilution of the sample and derivatization, analysis was on a HP-1 capillary column and a flame ionization detector was used to determine the bistrimethylsilyl derivative of fosfomycin. Response was linear in the range 50–5000 g mL^–1. The detection limit was about 10 g mL^–1. The within and between day coefficients of variation did not exceed 6%. The method was applied to the determination of fosfomycin in urine samples collected during clinical pharmacokinetic studies.     

磷霉素改性氧化锆固定相色谱性能研究

本文利用磷霉素与氧化锆表面的强Ｌｅｗｉｓ酸碱作用,分别采用静态和动态两种途径以磷霉素对自制ＺｒＯ２固定相进行改性,考察了改性前后固定相色谱性能的变化。通过磷霉素改性,能够较好地覆盖氧化锆表面存在的Ｌｗｅｉｓ酸活性中心点,从而减少对酸性化合物的不可逆吸附及拖尾现象。磷霉素动态改性氧化锆表现出一定的反相色谱性能,静态改性氧化锆则表现出较强的极性。     

A practical synthesis of （-）fosfomycin from its enantiomer

（＋）-cis-（1S, 2R）-Epoxypropylphosphonic acid, the enantiomer of fosfomycin, which is the industrial side-product in the preparation of the antibiotic fosfomycin, was converted into （-）fosfomycin by a seven-step procedure. The esterification of the dihydroxyphosphonic intermediate was the key step. The title compound was obtained in good yield and its optical purity was up to the medicine quality standard of Chinese Pharmacopoeia.     

Determination of fosfomycin in pus by capillary zone electrophoresis

A method is described for the determination of fosfomycin in pus by capillary zone electrophoresis with reversed electroosmotic flow, and indirect UV absorbance detection. Sample pre-treatment is limited to removal of proteins and cell debris by adding the double volume of methanol, followed by vortexing for few seconds, and centrifugation at 15,000 x g for 2 min. The supernatant is directly injected into the instrument. Fosfomycin is separated from sample constituents with a background electrolyte at pH 7.25 (25 mM benzoate buffer with 0.5 mM hexadecyltrimethylammonium bromide added, adjusted to pH with tris(hydroxymethyl)-aminomethane (TRIS)). Separation is carried out in a capillary with 50 microm I.D., 64.5 cm total length, 56.0 cm to the detector, at 25 degrees C with -25 kV voltage applied. Due to the low absorbance of the analyte, indirect UV detection was performed at 254 nm using a bubble cell capillary. Sample was injected by pressure (450 mbar s). Repeatability for fosfomycin in spiked pus (from 8 or 10 consecutive injections of three different series at concentrations of 100 microg/mL of the antibiotic) was between 2.4 and 8.2% relative standard deviation (RSD). Accuracy (expressed as recovery of fosfomycin determined by three independent analysis at 10, 100 and 300 microg/mL fosfomycin added to plain pus) was between 75 and 102%. Intermediate reproducibility (n = 9 at three different days) was between 2 and 12% RSD. Limit of detection and limit of quantitation were 4.5 and 15 microg/mL, respectively. The concentration of fosfomycin in pus of patients treated with the antibiotic ranged up to 240 microg/mL. The concentration of other anionic pus constituents identified beside chloride (acetate, succinate, lactate, phosphate) ranged between 20 and 7800 microg/mL.