Solid-state stability study of meropenem – solutions based on spectrophotometric analysis

Chemistry Central Journal

Judyta Cielecka-Piontek²  Magdalena Paczkowska²  Kornelia Lewandowska¹  Boleslaw Barszcz¹  Przemyslaw Zalewski²  Piotr Garbacki² 

[1] Department of Molecular Crystals, Institute of Molecular Physics Polish Academy of Sciences, Smoluchowskiego 17, Poznań, 60-179, Poland

[2] Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Poznan University of Medical Sciences, Grunwaldzka 6, Poznań, 60-780, Poland

关键词: Solid state;    Degradation;    Raman-spectroscopy;    FT-IR spectroscopy;    Derivative spectroscopy;    Meropenem;   

Others  :  787895
DOI  :  10.1186/1752-153X-7-98

 received in 2013-02-13, accepted in 2013-05-27,  发布年份 2013

【 摘 要 】

Background

B-Lactam antibiotics are still the most common group of chemotherapeutic drugs that are used in the treatment of bacterial infections. However, due to their chemical instability the potential to apply them as oral pharmacotherapeutics is often limited and so it is vital to employ suitable non-destructive analytical methods. Hence, in order to analyze such labile drugs as β-lactam analogs, the application of rapid and reliable analytical techniques which do not require transferring to solutions or using organic solvents, following the current green approach to pharmaceutical analysis, is necessary. The main objective of the present research was to develop analytical methods for the evaluation of changes in meropenem in the solid state during a stability study.

Results

The UV, FT-IR and Raman spectra of meropenem were recorded during a solid-state stability study. The optimum molecular geometry, harmonic vibrational frequencies, infrared intensities and Raman scattering activities were calculated according to the density-functional theory (DFT/B3LYP method) with a 6-31G(d,p) basis set. As the differences between the observed and scaled wavenumber values were small, a detailed interpretation of the FT-IR and Raman spectra was possible for non-degraded and degraded samples of meropenem. The problem of the overlapping spectra of meropenem and ring-containing degradation products was solved by measuring changes in the values of the first-derivative amplitudes of the zero-order spectra of aqueous solutions of meropenem. Also, molecular electrostatic potential (MEP), front molecular orbitals (FMOs) and the gap potential between highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) were determined.

Conclusions

Based on the findings of this work, it appears possible to use time-saving and reliable spectrophotometric analytical methods, supported by quantum-chemical calculations, for solid-state stability investigations of meropenem. The methods developed for this study may be considered a novel, green solution to pharmaceutical analysis of labile drugs – an alternative for the recommended chromatographic procedures.

【 授权许可】

   
2013 Cielecka-Piontek et al.; licensee Chemistry Central Ltd.

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