Impurity profiling of dexamphetamine sulfate by cyclodextrin‐modified microemulsion electrokinetic chromatography

Abstract

A CD-modified microemulsion electrokinetic chromatography method has been developed and validated for dexamphetamine sulfate which allows the simultaneous determination of charged and uncharged impurities of the drug including the levorotary (R)-enantiomer. The optimized background electrolyte consisted of 1.5% w/w SDS, 0.5% w/w ethyl acetate, 3.5% w/w 1-butanol, 2.5% w/w 2-propanol and 92% w/w 50 mM sodium phosphate buffer, pH 3.0, containing 5.5% w/w sulfated β-CD. Separations were performed in a 50.2/40 cm, 50 μm id fused silica capillary at a temperature of 20°C and an applied voltage of -14 kV. Carbamazepine was used as internal standard. The assay was validated in the range of 0.1-1.0% for the related substances and 0.1-5.0% for levoamphetamine based on a concentration of 3 mg/mL of dexamphetamine sulfate. The LOD of all analytes ranged between 0.05 and 0.2%. In commercial samples of dexamphetamine sulfate, levoamphetamine was found at concentrations between 3.2 and 3.8%, whereas none of the other impurities could be detected.

Chiral electromigration techniques in pharmaceutical and biomedical analysis

“…Analysis of commercial dexamphetamine samples revealed the presence of phenylacetone and phenylacetone oxime indicating that the investigated drug samples were synthesized from achiral precursor molecules and the resulting racemic amphetamine was resolved by fractional crystallization. The third assay used a microemulsion composed of 0.5% ethyl acetate, 1.5% SDS, 3.5% 1-butanol, 2.5% 2-propanol and 92% 50 mM sodium phosphate buffer, pH 3.0, and 5.5% sulfated β-CD as chiral selector under reversed polarity of the applied voltage [93]. This MEEKC method also allowed the simultaneous separation of uncharged and charged impurities including levoamphetamine.…”

“…The application of CE in drug impurity analysis has been summarized [79,80]. Table 1 clearly reflects the general trend that CDs are by far the most widely used chiral selectors although some studies utilized other additives such as BSA [81], maltodextrin [82], (+)-18C6H4 [83], ligand exchange [84] or the chiral ionic liquid ethylcholine bis(trifluoromethylsulfonyl) Baclofen α-CD (18 mM) 0.1 M sodium borate, pH 9.9, 1% acetonitrile 2-10 μg/ml, analysis of racemic bulk drug and tablets [103] Benzimidazole derivatives Chloroquine SBE-β-CD (30 mg/ml) 100 mM sodium phosphate, pH 2.5 0.02%, analysis of laboratory sample [108] Clopidogrel Sulfated β-CD (5%) 10 mM triethylamine/phosphoric acid 0.08-0.33 μg/ml, minor enantiomer and related substances [109] Dexamphetamine HDAS-β-CD (10 mg/ml) 0.1 M sodium phosphate buffer, pH 2.5 0.06%, minor enantiomer and charged related substances [91] Dexamphetamine Sulfated β-CD (25 mg/ml), SBE-β-CD (80 mg/ml) 50 mM sodium phosphate buffer, pH 2.5 0.01-0.02%, minor enantiomer and related substances [92] Dexamphetamine Sulfated β-CD (5.5%) 1.5% SDS, 0.5% ethyl acetate, 3.5% 1-butanol, 2.5% 2-propanol and 92% 50 mM sodium phosphate buffer, pH 3.0 0.05-0.2%, minor enantiomer and related substances [93] Econazole HP-γ-CD (40 mM) 50 mM SDS in 20 mM phosphate buffer, pH 8.0…”

Recent advances in capillary electrophoretic migration techniques for pharmaceutical analysis

“…Clemastine is a single stereoisomer drug but the CDs were not required for the separation of diastereomers of the drug but rather related substances such as the N ‐oxide or degradation products. The simultaneous analysis of (achiral) related substances as well as stereoisomeric impurities in MEEKC could be achieved by the addition of chiral selectors such as CDs to the microemulsion (also see discussion below) .…”

“…At a concentration of dexamphetamine sulfate of 5 mg/mL, the LODs of the impurities were in the range of 0.01–0.02% depending on the analyte using 1 R ,2 S ‐(−)‐ephedrine as IS. A comparable separation of all analytes could be achieved by CD‐modified MEEKC . In this case, the microemulsion was composed of 0.5% w/w ethyl acetate, 1.5% w/w SDS, 3.5% w/w 1‐butanol, 2.5% w/w 2‐propanol, and 92% w/w 50 mM sodium phosphate buffer, pH 3.0, containing 5.5% w/w sulfated β‐CD.…”

A review of developments in the methodology and application of microemulsion electrokinetic chromatography

“…similar compounds . A validated CD‐modified MEEKC ME was developed by Wongwan et al for the separation of dexamphetamine sulfate from its ( R )‐enantiomer. As a starting point, the basic ME was optimized before modification with CD.…”