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Cyclodextrin-based nonaqueous electrokinetic chromatography with UV and mass spectrometric detection: application to the impurity profiling of amiodarone.
Electrophoresis. 2008 Sep; 29(17):3575-81.E

Abstract

The potential of nonaqueous electrokinetic chromatography (NAEKC) using cyclodextrins (CD) for the analysis of basic drugs and related compounds was evaluated. Both UV absorbance and mass spectrometric (MS) detection were employed. Addition of neutral CD to the NA background electrolyte did not significantly enhance the separation of a test mixture of basic drugs, and no change in selectivity was observed. In contrast, anionic single-isomer-sulfated CD strongly added to the selectivity of the NAEKC system inducing an improved resolution among the test compounds and increasing the migration time window. The applicability of the NAEKC system using anionic CD is demonstrated by the profiling of a sample of the drug amiodarone that had been stored for 1 year at room temperature. Amiodarone is poorly soluble in water. NAEKC-UV analysis indicated the presence of at least seven impurities in the amiodarone sample. In order to identify these compounds, the NAEKC system was coupled directly to electrospray ionization (ESI) ion-trap MS. The total of detected impurities increased to 12 due to the added sensitivity and selectivity of MS detection. Based on the acquired MS/MS data, three sample constituents could be identified as 'known' impurities (British Pharmacopoeia), whereas for three unknown impurities molecular structures could be proposed. Estimated limits of detection for amiodarone using the NAEKC method were 1 microg/mL with UV detection and 15 ng/mL with ESI-MS detection (full-scan). Based on relative responses, the impurity content of the stored drug substance was estimated to be 0.33 and 0.47% using NAEKC-UV and NAEKC-ESI-MS, respectively.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Mol R
Biomedical Analysis, Utrecht University, Utrecht, The Netherlands.
de Jong GJ
No affiliation info available
Somsen GW
No affiliation info available

MeSH

AmiodaroneAnti-Arrhythmia AgentsChromatography, Micellar Electrokinetic CapillaryCyclodextrinsMass SpectrometrySpectrophotometry, Ultraviolet

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18803218

Citation

Mol, Roelof, et al. "Cyclodextrin-based Nonaqueous Electrokinetic Chromatography With UV and Mass Spectrometric Detection: Application to the Impurity Profiling of Amiodarone." Electrophoresis, vol. 29, no. 17, 2008, pp. 3575-81.
Mol R, de Jong GJ, Somsen GW. Cyclodextrin-based nonaqueous electrokinetic chromatography with UV and mass spectrometric detection: application to the impurity profiling of amiodarone. Electrophoresis. 2008;29(17):3575-81.
Mol, R., de Jong, G. J., & Somsen, G. W. (2008). Cyclodextrin-based nonaqueous electrokinetic chromatography with UV and mass spectrometric detection: application to the impurity profiling of amiodarone. Electrophoresis, 29(17), 3575-81. https://doi.org/10.1002/elps.200800074
Mol R, de Jong GJ, Somsen GW. Cyclodextrin-based Nonaqueous Electrokinetic Chromatography With UV and Mass Spectrometric Detection: Application to the Impurity Profiling of Amiodarone. Electrophoresis. 2008;29(17):3575-81. PubMed PMID: 18803218.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cyclodextrin-based nonaqueous electrokinetic chromatography with UV and mass spectrometric detection: application to the impurity profiling of amiodarone. AU - Mol,Roelof, AU - de Jong,Gerhardus J, AU - Somsen,Govert W, PY - 2008/9/23/pubmed PY - 2008/11/5/medline PY - 2008/9/23/entrez SP - 3575 EP - 81 JF - Electrophoresis JO - Electrophoresis VL - 29 IS - 17 N2 - The potential of nonaqueous electrokinetic chromatography (NAEKC) using cyclodextrins (CD) for the analysis of basic drugs and related compounds was evaluated. Both UV absorbance and mass spectrometric (MS) detection were employed. Addition of neutral CD to the NA background electrolyte did not significantly enhance the separation of a test mixture of basic drugs, and no change in selectivity was observed. In contrast, anionic single-isomer-sulfated CD strongly added to the selectivity of the NAEKC system inducing an improved resolution among the test compounds and increasing the migration time window. The applicability of the NAEKC system using anionic CD is demonstrated by the profiling of a sample of the drug amiodarone that had been stored for 1 year at room temperature. Amiodarone is poorly soluble in water. NAEKC-UV analysis indicated the presence of at least seven impurities in the amiodarone sample. In order to identify these compounds, the NAEKC system was coupled directly to electrospray ionization (ESI) ion-trap MS. The total of detected impurities increased to 12 due to the added sensitivity and selectivity of MS detection. Based on the acquired MS/MS data, three sample constituents could be identified as 'known' impurities (British Pharmacopoeia), whereas for three unknown impurities molecular structures could be proposed. Estimated limits of detection for amiodarone using the NAEKC method were 1 microg/mL with UV detection and 15 ng/mL with ESI-MS detection (full-scan). Based on relative responses, the impurity content of the stored drug substance was estimated to be 0.33 and 0.47% using NAEKC-UV and NAEKC-ESI-MS, respectively. SN - 0173-0835 UR - https://www.unboundmedicine.com/medline/citation/18803218/Cyclodextrin_based_nonaqueous_electrokinetic_chromatography_with_UV_and_mass_spectrometric_detection:_application_to_the_impurity_profiling_of_amiodarone_ DB - PRIME DP - Unbound Medicine ER -