Comprehensive profiling of the complex dendrimeric contrast agent Gadomer using a combined approach of CE, MS, and CE‐MS

Abstract

The complex dendrimeric contrast agent Gadomer has been comprehensively characterized using various mass spectrometric techniques in combination with capillary electrophoresis. The analytical challenges arising from the structure of this analyte, e.g., the presence of a complex isotopic pattern originating from multiple gadolinium chelates could be overcome using this combined approach. Results obtained from initial MALDI-TOF-MS measurements could subsequently be complemented and confirmed by CE-ESI-TOF-MS measurements. Furthermore, high resolution Fourier transform-ion cyclotron resonance-MS (FT-ICR-MS) as a stand alone technique and in combination with CE was performed to obtain mass spectra of high mass accuracy and resolution of various impurities and related dendrimers present in low concentrations in several Gadomer batches. The profile of related dendrimers and impurities of lower molecular weight present in Gadomer could be elucidated and variances in the pattern of related dendrimers present in batches obtained via different synthetic routes could be detected. The qualitative analysis of Gadomer using MS techniques in combination with CE provides the fundamental basis for a framework of analytical methodologies for the characterization of Gadomer. By designing such a framework of methodologies the challenges associated with the introduction of dendrimers into the clinical stage may be overcome and the reproducible quality and safety of these innovative products can be ensured.

Characterization of polyamidoamino (PAMAM) dendrimers using in-line reversed phase LC electrospray ionization mass spectrometry

“…Therapeutic and experimental drugs 1–4 , dyes 5, 6 , solubilizing chains 7 or a mixture of all three 8 can subsequently be added to these functional groups creating powerful multi-functional biological agents. There exist a large number of scientific reports regarding the therapeutic potential of dendrimers and especially polyamidoamino (PAMAM) dendrimers 9–12 .…”

“…Direct analysis of PAMAM dendrimers by MALDI 6, 18–22 and ESI 2, 23 has also been reported. While these techniques are useful they are not sufficient for evaluating the purity, stability and detecting individual components of complex dendrimer mixtures.…”

Poly Ethoxy Ethyl Glycinamide (PEE‐G) Dendrimers: Dendrimers Specifically Designed for Pharmaceutical Applications

“…Robust measurement of the purity of dendrimers is challenging . Mass spectrometric data are useful for showing the presence of impurities if a good method has been developed that shows a strong resolved molecular ion, but is not a good tool to accurately quantify impurities .…”

A critical review on the use of modern sophisticated hyphenated tools in the characterization of impurities and degradation products

“…Another study is reported where CE-MS variants were used for the separation of gadomer, a dendrimeric contrast agent, from its related substances [207]. Initial mass measurements of low molecular weight IMPs were carried out using MALDI-TOF-MS, which were complimented and confirmed by CE-ESI-TOF-MS and CE-ESI-FT-ICR-MS.…”