Monitoring dynamic pre-crystallization aggregation processes in solution by VT-DOSY NMR spectroscopy

Equimolar mixtures of pyridine (Py) with para-halotetrafluoro-pyridine (BrTFP and ITFP) were investigated by VT-diffusion NMR experiments. The formation of a halogen-bond-stabilized ITFP·Py complex was de¬tected upon cooling a solution in...

Stability Evaluation and Degradation Studies of DAC® Hyaluronic-Polylactide Based Hydrogel by DOSY NMR Spectroscopy

The stability and the degradation of polymers in physiological conditions are very important issues in biomedical applications. The copolymer of hyaluronic acid and poly-D,L-lactic acid (made available in a product called DAC®) produces a hydrogel which retains the hydrophobic character of the poly-D,L-lactide sidechains and the hydrophilic character of a hyaluronic acid backbone. This hydrogel is a suitable device for the coating of orthopedic implants with structured surfaces. In fact, this gel creates a temporary barrier to bacterial adhesion by inhibiting colonization, thus preventing the formation of the biofilm and the onset of an infection. Reabsorbed in about 72 h after the implant, this hydrogel does not hinder bone growth processes. In the need to assess stability and degradation of both the hyaluronan backbone and of the polylactic chains along time and temperature, we identified NMR spectroscopy as a privileged technique for the characterization of the released species, and we applied diffusion-ordered NMR spectroscopy (DOSY-NMR) for the investigation of molecular weight dispersion. Our diffusion studies of DAC® in physiological conditions provided a full understanding of the product degradation by overcoming the limitations observed in applying classical chromatography approaches by gel permeation UV.

Application of 1H DOSY NMR in Measurement of Polystyrene Molecular Weights

In this work, we studied the applicability of diffusion ordered nuclear magnetic resonance spectroscopy (DOSY NMR) as an alternative method in determination of polystyrene molecular weight. DOSY NMR spectroscopy allows measuring the diffusion coefficient of molecule which directly depend on hydrodynamic radius and so on, average molar mass in weight (Mw). By using commercial polystyrene (PS) standards, an external calibration curve was established. Based on the excellent linear correlation between diffusion coefficient (logD) and molecular weight (logM), the molecular weight of polystyrene can be predicted using the following equation . The validation was done by comparing with the Mw value obtained by gel permeation chromatography within less than 5% deviation. From the diffusion coefficient, some property of polystyrene in solution, such as Flory coefficient and polymer-solvent interaction, were also studied. The Flory coefficient confirmed that chloroform is a good solvent for PS.

Determination of d-Cycloserine Impurities in Pharmaceutical Dosage Forms: Comparison of the International Pharmacopoeia HPLC–UV Method and the DOSY NMR Method

d-cycloserine is a broad-spectrum antibiotic that is currently being used as a secondary choice in the treatment of tuberculosis. In recent years, it has become more popular, due to its effect on the nervous system. In this current study, we provide evidence that The International Pharmacopoeia HPLC–UV method for d-cycloserine impurity profiling is not repeatable due to the variable response of cycloserine dimer, one of d-cycloserine impurities. Therefore, we introduced the DOSY (diffusion ordered spectroscopy) NMR (nuclear magnetic resonance) technique to determine the levels of d-cycloserine impurities in pharmaceutical dosage forms. The DOSY NMR technique allowed separation of d-cycloserine, its degradation products, and key process impurities in concentrations below pharmacopoeial specification limits. The proposed DOSY NMR method allowed accurate identification and quantification of the cycloserine dimer, which was not possible through the use of the pharmacopoeial HPLC method. The current method has the potential for practical use in analytical laboratories of the pharmaceutical industry.

QUALITY ASSESSMENT AND QUANTIFICATION OF GENISTEIN IN DIETARY SUPPLEMENTS BY HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY, QUANTITATIVE NUCLEAR MAGNETIC RESONANCE, AND TWO-DIMENSIONAL DIFFUSION ORDERED SPECTROSCOPY 1H

Objective: The aim of the present study is to analyze four herbal dietary supplements containing genistein by liquid chromatography, quantitative nuclear magnetic resonance (qNMR), and diffusion ordered spectroscopy (DOSY) 1H NMR. Methods: Quantification of the active ingredient, genistein, is carried out by high-performance liquid chromatography (HPLC) and qNMR. Two-dimensional (2D) DOSY NMR also allows the qualitative analysis of the samples with the detection of active ingredient and excipients present in the formulations. Results: The validated HPLC and qNMR methods showed that all four supplements contain genistein in different amounts, and 2D DOSY NMR provides a clear image of all ingredients in the formulations. Conclusion: The use of the three techniques provides detailed information on each product and its contents, and all of them are currently used for the quality control of natural supplements by our laboratory.