Meropenem Exists in Equilibrium with a Carbon Dioxide Adduct in Bicarbonate Solution

Almarsson, Ӧrn; Kaufman, Michael J.; Stong, John D.; Wu, Yunhui; Mayr, S; Petrich, Mark A.; Williams, J. M.

doi:10.1021/js970370u

Cited by 22 publications

(17 citation statements)

References 15 publications

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“…41,42 For carbapenems, mainly meropenem, some works have described the NMR analysis to characterize the antibiotic, the degradation products and impurities. [15][16][17]43 In the present work, the chemical structure of doripenem ( Figure 1) was confirmed based on the signals obtained in the spectra. The 1 H and 13 C NMR data were interpreted and the results are showed in Table 2.…”

Section: Nmrsupporting

confidence: 75%

“…11,12 For other carbapenems, the works also focus on quantitation by LC, UV spectrophotometry and microbiological assay, applied on stability studies. [13][14][15] For meropenem, Almarsson et al 16 reports the analysis of the drug by proton and 13-carbon NMR coupled with tandem mass spectroscopy, which showed evidence that the structure is stable as CO 2 adduct, in solid state and in solution. Nishimura et al 17 describes the structural analysis of meropenem by 1 H NMR and X-ray diffraction, comparing to other penems and carbapenems.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of the antibiotic doripenem using physicochemical methods: chromatography, spectrophotometry, spectroscopy and thermal analysis

et al. 2011

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Recebido em 1/11/10; aceito em 14/5/11; publicado na web em 22/7/11 Doripenem was characterized through physicochemical and spectroscopic techniques, as well as thermal analysis. TLC (Rf = 0.62) and HPLC (rt = 7.4 min) were found to be adequate to identify the drug. UV and infrared spectra showed similar profile between doripenem bulk and standard. The 1 H and 13 C NMR analysis revealed chemical shifts that allowed identifying the drug. Thermal analysis demonstrated three steps with mass loss, at 128, 178 and 276 o C. The work was successfully applied to qualitative analysis of doripenem, showing the reported methods can be used for physicochemical characterization of doripenem.

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Section: Nmrsupporting

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Characterization of the antibiotic doripenem using physicochemical methods: chromatography, spectrophotometry, spectroscopy and thermal analysis

et al. 2011

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“…It had been previously reported that the degradation of carbapenem antibiotics, imipenem and meropenem, followed a pseudo-first-order degradation in an aqueous solution, and the initial concentration was considered to affect the degradation of the drugs. [7][8][9][10][11] However, the mechanism of how the concentration affected the degradation had not been elucidated.…”

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confidence: 99%

Effect of Initial Concentration on Stability of Panipenem in Aqueous Solution

Ito

Suzuki

Kusai

et al. 2005

CHEMICAL & PHARMACEUTICAL BULLETIN

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Panipenem (PAPM,, Fig. 1), which was discovered and developed in Sankyo Co., Ltd., is a carbapenem antibiotic with a broad antibacterial spectrum and potent bactericidal activity. [1][2][3][4][5] In the previous report, the degradation kinetics of panipenem in aqueous solution at a fixed initial panipenem concentration (5 mg/mlϷ15 mM) was studied with regards to pH, temperature, ionic strength, and buffer catalysis.6) The degradation of panipenem followed first-order kinetics, and the pH dependence of the apparent first-order rate constants was explained using the specific acid-base catalysis theory and considering the dissociation of the carboxyl group.In the study reported here, the effect of panipenem concentration on the degradation of panipenem was investigated. It had been previously reported that the degradation of carbapenem antibiotics, imipenem and meropenem, followed a pseudo-first-order degradation in an aqueous solution, and the initial concentration was considered to affect the degradation of the drugs.7-11) However, the mechanism of how the concentration affected the degradation had not been elucidated.In this report, we investigated the effect of the initial panipanem concentration on the degradation of panipenem, in particular, in an acidic solution. ExperimentalMaterials Panipenem was obtained from lots produced in-house (Sankyo Co., Ltd.) and used without further purification. 2-(N-Morpholino) ethanesulfonic acid (MES, pK a ϭ6.15) and 3-(N-Morpholino) propanesulfonic acid (MOPS, pK a ϭ7.20) were purchased from Dojin Chemicals Co., Ltd. All the other chemicals used were of reagent grade.Kinetic Runs Aqueous buffer solutions were adjusted to the desired pH with concentrated aqueous sodium hydroxide or diluted hydrochloric acid. The buffer species used were, citrate (pH 2.0-4.5), MES (pH 5.0-6.5), MOPS (pH 7.0-8.0), and carbonate (pH 8.5-10.0). Then, panipenem was weighed and added to the buffered solutions. These buffered solutions were placed in test tubes and maintained at the reaction temperatures in a thermostatic water bath (Ϯ0.1°C). The pH values of these buffered solutions were measured with a pH electrode at every sampling time point to confirm to be within desired pH Ϯ0.1. If the pH value deviated, the pH value was re-adjusted by concentrated aqueous sodium hydroxide or diluted hydrochloric acid, and then the kinetic run was continued. The samples in the test tubes were periodically analyzed, and the residual panipenem concentrations were determined by high performance liquid chromatography (HPLC). In citrate and carbonate buffers, the buffer concentration effects on the rate constants were observed, so the rate constants were obtained by extrapolating the buffer concentration to zero. In MES and MOPS buffers, the concentration effects were not observed, so the experiments were conducted at the buffer concentration of 0.2 M or 0.5 M, and these buffers showed the sufficient buffer index during the kinetic runs. As for the ionic strength of the solution, it was shown that the ionic streng...

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“…6. (11) In Eq. 11, A is the frequency factor, E a is the activation energy, R is the gas constant (Rϭ1.987 cal mol Ϫ1 K…”

Section: Resultsmentioning

confidence: 99%

“…[5][6][7][8][9][10][11] As for its stereochemistry, panipenem exists as either the Z-form or E-form depending on the position of the acetimidoyl group. 12) A certain isomer type can be obtained depending on the solvent used in the recrystallization process; the E/Z mixture, E-form, and Z-form can be obtained, by using acetone, methanol, and ethanol as the recrystallization solvent, respectively.…”

mentioning

confidence: 99%