Capillary electrophoresis‐mass spectrometry in impurity profiling of pharmaceutical products

Abstract

Generally reversed-phase high-performance liquid chromatography (RP-HPLC) methods are extensively applied during quality control of pharmaceutical products. Since capillary electrophoresis (CE) is based on a different separation principle and consequently results in a unique selectivity compared to RP-HPLC, it can advantageously be used as an orthogonal technique. CE equipped with a mass spectrometer detector provides even more information that can be helpful for identification and structural elucidation purposes. CE-MS was recently implemented in the method development approach to support impurity profiling of pharmaceutical products. In this paper the application of CE-electrospray ionization (ESI)-MS/MS to the impurity profiling of galantamine hydrobromide in stressed Reminyl Extended Release (ER) capsules is discussed. Reminyl ER samples were stressed at different storing conditions. The impurity profile of these samples was compared with the current RP-HPLC and chiral CE method, but also with CE-ESI-MS/MS. The combination of these three methods provided valuable data that allowed understanding comprehensively the impurity profile of these samples. Two impurities were detected at concentrations lower than 0.05%, which did not occur in nonstressed samples. Chromatographic data and the fragmentation patterns of galantamine and related compounds were also examined for identification of these two degradation products.

Recent advances in the application of capillary electrophoresis with mass spectrometric detection

“…Impurity profiling of pharmaceutical products by CE-MS/ MS has been presented by Visky et al [119]. In their work they investigated the changes in composition of a pharmaceutical formulation after stressing it for 18 months at Abbreviations: APPI, atmospheric pressure photo ionization; NMF, N-methylformamide; DIKGA, (2) 2,3,4,6-Di-O-isopropylidene-2-keto-L-gluconic acid; MRI, magnetic resonance imaging; HS-g-CD, highly sulfated g-CD.…”

Comparison of atmospheric pressure photoionization and ESI for CZE‐MS of drugs

“…This can be explained by the fact that both CZE and ESI usually deal with analytes that are (or can be) ionized in solution. Numerous successful applications of CZE-ESI-MS have been reported, including stability studies [4] and impurity profiling of drugs [5,6], and the analysis of drugs in biological samples [7]. Nevertheless, the use of ESI for CZE-MS has an inherent drawback.…”

Impurity analysis of pharmaceuticals using capillary electromigration methods

“…Another set of capsules was stressed under different conditions to verify the stability indicating assay capability of the methods. The best separation was achieved using RPLC; however, the information obtained from CZE analyses was used to verify the suitability of RPLC for the assay of galantamine and its impurities [86].…”