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.
Article: Kinetics of Degradation of Biapenem[Show abstract] [Hide abstract]
ABSTRACT: The kinetic and thermodynamic analysis of biapenem degradation was conducted during acid–base hydrolysis, under the influence of buffer components and in the solid state at increased temperature (dry air) and relative air humidity (RH > 50%). The effects of the initial concentration of biapenem and the formation of degradation products on its stability were investigated.International Journal of Chemical Kinetics 08/2014; 46(8). DOI:10.1002/kin.20860 · 1.57 Impact Factor
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ABSTRACT: The kinetic and thermodynamic parameters of degradation of doripenem were studied using a high‐performance liquid chromatography method. In dry air, the degradation of doripenem was a first‐order reaction depending on the substrate concentration. At increased relative air humidity, doripenem was degraded according to the autocatalysis kinetic model. The dependence ln k = f1/T) was described by the equations ln k = 5.10 ± 13.06 − (7576 ± 4939)(1/T) in dry air and ln k = 46.70 ± 22.44 − (19,959 ± 8031)(1/T) at 76.4% relative humidity (RH). The thermodynamic parameters E a, ΔH ≠a, and ΔS ≠a of the degradation of doripenem were calculated. The dependence ln k = f (RH%) was described by the equation ln k = (0.155 ± 0.077) × 10−1 (RH%) − (3.45 ± 21.8) × 10−10. © 2012 Wiley Periodicals, Inc. Int J Chem Kinet 44: 722–728, 2012International Journal of Chemical Kinetics 11/2012; 44(11). DOI:10.1002/kin.20722 · 1.57 Impact Factor
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ABSTRACT: Carbapenems, including meropenem and imipenem, exhibit low stability against acid or base reagents. The fragmentation behavior of meropenem and its acid hydrolysis products was investigated by Fourier transform ion cyclotron resonance electrospray ionization tandem mass spectrometry and ion trap tandem multi-stage mass spectrometry in both positive and negative ion mode. Only one neutral loss of CO(2) was observed from the precursor ion to the MS(4) product ions for the acid hydrolysis product and this behavior did not correspond to that expected for the previously accepted 1-pyrroline or 2-pyrroline structure with two carbonyl acid units. The unknown product was then proposed to be 2-(4-(5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-5-imino-3-methyl-6-oxotetrahydro-2H-pyran-2-yl)-3-hydroxybutanoic acid on the basis of the multi-stage mass spectrometric and accurate mass data. A similar acid hydrolysis product of imipenem was also identified by mass spectrometry, confirming that these carbapenems had the same acid hydrolysis behavior. The proposed structures were further confirmed by NMR experiments.Rapid Communications in Mass Spectrometry 10/2009; 23(19):3205-12. DOI:10.1002/rcm.4240 · 2.64 Impact Factor