Quantitative ³¹ P-NMR spectroscopy for the determination of fosfomycin and impurity A in pharmaceutical products of fosfomycin sodium or calcium

Abstract

A quantitative 31P-NMR method for the determination of fosfomycin and impurity A in pharmaceutical products of fosfomycin sodium or calcium has been developed. In this method, coaxial inserts containing trimethyl phosphate are used as external standard. The method is convenient and robust, and gives both high accuracy and precision. It is shown that an accurate determination is possible using different probes and coaxial inserts.

Physicochemical and Antimicrobial Properties of Thermosensitive Chitosan Hydrogel Loaded with Fosfomycin

“…Assignments of FOS signals (no CH) are shown in Figure S3. The relative signal intensities from integration ( Figure 6B) are comparable to that observed for the sample lacking CH ( Figure S3) and peak assignments agree with Jiang et al [19].…”

“…The 31 P NMR revealed a substantially weaker signal for native (~10 ppm) and ring-opened (~16 ppm) FOS, but a signal for phosphate buffer (~-2 ppm) was still observed ( Figure S3). The (DOSY) experiments were performed [18,19] in water and in the CH matrix, both with D2O. While peaks were very broad and had low signal to noise in the hydrogel, fitting three independent aliphatic FOS peaks yielded an apparent translational diffusion coefficient of (6.2 ± 0.9) x 10 −10 m 2 s −1 , where the uncertainty is the standard error of the mean (Figure 7).…”

“…Each 31 P-NMR spectrum was recorded at 298 K using an inverse-gated decoupling pulse sequence, with 128 scans, a spectral width of 38 ppm, an acquisition time of 1 s, and a recycle delay of 4 s. The native and ring-opened 31 P signals of FOS were assigned by monitoring the NMR spectra of a pH 2.5 sample by adding 1 M HCl to lower the pH. Diffusion ordered spectroscopy (DOSY) experiments were performed in triplicate, with samples taken from independent peaks in the spectra, and recorded as an interleaved set of 25 experiments, with gradient powers ranging from 1-47 G/cm [18,19]. Water suppression in DOSY experiments was obtained with 4 s of presaturation during the recycle delay.…”

The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research

“…In either of the first two cases the only significant degradation product arises from opening the epoxide ring to give a mixture of the (1 S ,2 S and 1 R ,2 R ) diols 106a and 106b , collectively referred to as “impurity A”. The lack of UV absorbance and the high hydrophilicity of these compounds confounds the usual HPLC quality analysis procedures and Jiang et al have developed a quantitative 31 P NMR (qP NMR) method circumventing these problems 325 …”

Quantitative NMR Studies of Multiple Compound Mixtures

“…Similarly, a study was reported on qualitative and quantitative analysis of rilmenidine dihydrogen phosphate (RLM) and its relative impurity-B by using 1 H qNMR [173]. In addition, 31 P qNMR was also used to determine fosfomycin (FOSF) and impurity A in pharmaceutical products of FOSF sodium or calcium [177], and coeluting impurity in a modified oligonucleotide [184]. Besides the aforementioned main applications of qNMR in pharmaceutical research, qNMR can also be applied to counterfeit analysis [192] and evaluation of drug delivery systems, such as in vitro drug release test [193], analysis of skin penetration of active drug [194,195].…”