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

Abstract

BackgroundB-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.ResultsThe 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.ConclusionsBased 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.

The Radiostability of Meropenem Trihydrate in Solid State

“…For the 25 kGy irradiation dose, there were no changes in the position and intensity of the characteristic bands of meropenem. In our previous studies, we defined the characteristic bands of MRP based on the DFT (density functional theory) method [ 18 ], and then we analyzed the changes especially in relation to the bands corresponding to the labile bonds. The most significant bands that did not change their intensity and location are attributed to stretching and bending vibrations of O-H bonds in the carboxylic group, deformation vibrations of pyrrolidine ring, stretching and bending vibrations of the N-C bond in the β-lactam ring, stretching and scissoring vibrations of bonds in the dimethylcarbomoyl group, and stretching vibrations of C-H bonds in the hydroxyethyl group.…”

“…Authors also suggest that the decrease in microbiological activity of clinical isolates may be influenced by changes within the trans-hydroxyethyl group. The configuration of the trans-hydroxyethyl group is associated with the resistance of meropenem to selected bacterial strains ( Table 2 ) [ 18 ].…”

Evaluation of the Chemical Integrity of Beta-Lactam Antibiotics by Iodine-Based Assay

“…A reliable, simple, and quantitative analytical method for the determination of β-lactam integrity is therefore necessary to control the degree of degradation of these antibiotics. Most, if not all, analytical methods for integrity analysis of β-lactam analogs were developed based on the surveying of spectrophotometric properties in a visible and ultraviolet radiation range [5]- [12]. The desired signals were possible to obtain by measurement of either direct absorption or of the absorption of the resulting species of an analyte/derivatizing reagent reaction [5]- [13].…”

“…Various modifications of the original method have been introduced for specific assays required for different β-lactam antibiotics [4], being predominantly focused on a quantitative estimate of β-lactamase activity [4]. In general, quality control for the chemical integrity of this kind of antibiotics has been assigned to more sophisticated methods, such as mass spectroscopy, liquid chromatography, and vibrational spectroscopy (RAMAN, FTRI) [5] [13] [14]. However, in spite of the high accuracy and high resolution of these methods, they remain expensive, require professional training, and need special samples to be prepared for such fixed-time assay.…”

“…This is why the search for new analytical methods, especially convenient, time-fixed, and inexpensive ones, is very important. Specifically, spectrophotometric properties of β-lactam analogs (with accuracy and selectivity enhanced by chemometric procedures) have been gaining significant interest [5]- [12]. In this report, we describe a modification of the original iodometric method [4] that allows for the detection of degradation in β-lactam antibiotic products with integrity of less than 90%.…”