The stability of biapenem and structural identification of impurities in aqueous solution.
ABSTRACT The stability of biapenem in aqueous solution was investigated. Forced degradation of biapenem was carried out under different concentrations, pH values and temperatures. The degradation products were determined by reverse-phase HPLC and identified by LC-MS/MS. One dimeric impurity was obtained by reverse-phase preparative HPLC and characterized by LC-MS/MS and NMR. A possible degradation mechanism has been presented.
- SourceAvailable from: Teodoro S Kaufman[Show abstract] [Hide abstract]
ABSTRACT: Current standards and regulations demand the pharmaceutical industry not only to produce highly pure drug substances, but to achieve a thorough understanding of the impurities accompanying their manufactured drug substances and products. These challenges have become important goals of process chemistry and have steadily stimulated the search of impurities after accelerated or forced degradation procedures. As a result, impurity profiling is one of the most attractive, active and relevant fields of modern pharmaceutical analysis. This activity includes the identification, structural elucidation and quantitative determination of impurities and degradation products in bulk drugs and their pharmaceutical formulations. Nuclear magnetic resonance (NMR) spectroscopy has evolved into an irreplaceable approach for pharmaceutical quality assessment, currently playing a critical role in unequivocal structure identification as well as structural confirmation (qualitative detection), enabling the understanding of the underlying mechanisms of the formation of process and/or degradation impurities. NMR is able to provide qualitative information without the need of standards of the unknown compounds and multiple components can be quantified in a complex sample without previous separation. When coupled to separative techniques, the resulting hyphenated methodologies enhance the analytical power of this spectroscopy to previously unknown levels. As a result, and by enabling the implementation of rational decisions regarding the identity and level of impurities, NMR contributes to the goal of making better and safer medicines. Herein are discussed the applications of NMR spectroscopy and its hyphenated derivate techniques to the study of a wide range pharmaceutical impurities. Details on the advantages and disadvantages of the methodology and well as specific challenges with regards to the different analytical problems are also presented.Journal of Pharmaceutical and Biomedical Analysis 04/2014; · 2.95 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: NR2B9c (Lys-Leu-Ser-Ser-Ile-Glu-Ser-Asp-Val) is a 9-amino acid peptide that has been illustrated to be a potential anti-stroke drug. For more effective treatment, suitable drug delivery systems should be developed. However, little is known about the stability of NR2B9c which is essential to its formulation. In this study, a reversed-phase high-performance liquid chromatography (HPLC) was applied to study the forced degradation behavior and stability of NR2B9c. HPLC studies were performed with an C8 column using a mobile phase consisting of acetonitrile (14.5:85.5, v/v) and aqueous solution (0.1% trifluoroacetic acid (TFA) and 0.05M KH2PO4). The flow rate and the wavelength set during HPLC detection were 1.0mL/min and 205nm, respectively. The degradation pattern of NR2B9c aqueous solution followed pseudo first-order kinetics. The degradation rate at pH 7.5 was the slowest according to the plotting V-shaped pH-rate profile. The influence of temperature on the rate of reactions was interpreted in terms of Arrhenius equation (r(2)>0.98). Thermodynamic parameters were calculated based on Eyring equation (r(2)>0.98). The concentrations of drug, buffer species, buffer concentrations, oxidation and organic solvents have noticeable effects on the degradation of NR2B9c while ultrasound shows little impact under the experimental conditions. In a word, this study may give a detailed description of stability of NR2B9c.International journal of pharmaceutics. 06/2014;
- [Show abstract] [Hide abstract]
ABSTRACT: A validated high-performance liquid chromatography-diode array detector (HPLC-DAD) method for stability studies of tebipenem pivoxil was developed. The separation of tebipenem pivoxil in the presence of main degradation product-tebipenem-was achieved by using a LiChrospher C-18 column (5 µm, 250 × 4.6 mm) with the mobile phase containing a mixture of 50 mmol L(-1) ammonium acetate-acetonitrile-triethylamine (68 : 30 : 2, v/v/v) adjusted to pH 3.5 with concentrated phosphoric acid (V). The column effluent was monitored by a photodiode array detector at 330 nm. The flow rate was 0.8 mL min(-1). Tebipenem pivoxil was subjected to degradation in aqueous solutions (acid-base hydrolysis, oxidation) and in the solid state (photolysis, thermolysis at an increased relative humidity and in dry air). The validated HPLC method was successfully applied to investigate the kinetics of conversion of tebipenem pivoxil to tebipenem (main metabolite). The other degradation products of tebipenem pivoxil were also monitored.Journal of chromatographic science 06/2014; · 0.79 Impact Factor