Cyclodextrin‐based nonaqueous electrokinetic chromatography with UV and mass spectrometric detection: Application to the impurity profiling of amiodarone

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.

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

“…Although there was decrease in sensitivity of the detection in mass by direct coupling, still the technique could be used for the identification and characterization of minor IMPs. Similarly, impurity profiling of amiodarone was carried out using non-aqueous electrokinetic chromatography coupled to MS by employing anionic cyclodextrin as the pseudo-stationary phase (PSP) [206].…”

Determination of impurities and counterions of pharmaceuticals by capillary electromigration methods

“…CE methods have been applied for the impurity studies of the drugs with various types of pharmacological activities such as chemotherapeutic agents , cardiovascular drugs , antithrombotics , antihistaminic drugs , corticosteroids , analgesics , anaesthetics , antidepressants , central nervous system drugs , antimuscarinics , antibiotics , antiviral drugs , and antimalarial drugs . CE methods are increasingly being viewed as an alternative and/or complement to HPLC for analysis of various types of impurities observed during the drug production or storage.…”

“…An antiarrhythmic agent, amiodarone, used in the treatment of ventricular and supraventricular tachycardia, and its degradation products were analyzed using nonaqueous EKC with UV or MS detection with 10 mM ammonium formate, 0.75 M formic acid and 10 mM heptakis(2,3‐di‐ O ‐acetyl‐6‐ O ‐sulfo)‐β‐CD as BGE . Compared to UV, significant improvement in selectivity and sensitivity was observed employing ESI‐MS detection, allowing detection of impurities below 0.01% .…”

Chiral Separations by Capillary Electrophoresis

“…Mol et al described the coupling of NACE with mass spectrometric detection for both chiral and nonchiral applications [137][138][139]. A setup was presented that used anionic CDs HDAS-β-CD and HDMS-β-CD, as chiral selectors [137].…”

“…Five NSAIDs could be enantioseparated using this approach, with Rs values between 0.9 and 2.2. A CD-based method was used for the separation of several nonchiral drugs, including an artificial test mixture and a one-year-old amiodarone sample [139]. Briefly, it was mentioned that HDMS-β-CD showed some enantioselectivity for atropine, the only chiral drug in the set of compounds investigated.…”