Separation of ephedrine and pseudoephedrine enantiomers using a polysaccharide‐based chiral column: A normal phase liquid chromatography–high‐resolution mass spectrometry approach

Abstract

Chiral considerations are found to be very much relevant in various aspects of forensic toxicology and pharmacology. In forensics, it has become increasingly important to identify the chirality of doping agents to avoid legal arguments and challenges to the analytical findings. The scope of this study was to develop an liquid chromatography–mass spectrometry (LCMS) method for the enantiomeric separation of typical illicit drugs such as ephedrines (ie, 1S,2R(+)‐ephedrine and 1R,2S(−)‐ephedrine) and pseudoephedrine (ie, R,R(−)‐pseudoephedrine and S,S(+)‐pseudoephedrine) by using normal phase chiral liquid chromatography–high‐resolution mass spectrometry technique. Results show that the Lux i‐amylose‐1 stationary phase has very broad and balancing‐enantio‐recognition properties towards ephedrine analogues, and this immobilized chiral stationary phase may offer a powerful tool for enantio‐separation of different types of pharmaceuticals in the normal phase mode. The type of mobile phase and organic modifier used appear to have dramatic influences on separation quality. Since the developed method was able to detect and separate the enantiomers at very low levels (in pico grams), this method opens easy access for the unambiguous identification of these illicit drugs and can be used for the routine screening of the biological samples in the antidoping laboratories.

Study on Quality Control of Tenofovir Disoproxil Fumarate Enantiomers by High-Performance Liquid Chromatography–Mass Spectrometry

“…The separation is thought to be achieved by the formation of hydrogen bonds between the -NH or -CO groups on the carbamate structure and the analyte, as well as by π-π and van der Waals interactions with the benzene ring. The carbamate bond is around the cavity of the main chain of polysaccharide, providing more flexibility to the benzene ring, thus the cavity can be adjusted for different analytes, and the π-π interaction can be maximized [23]. The (R)-TDF and (S)-enantiomer contain C = O and -NH functional groups, which can form hydrogen bonds with carbamates in amylose-tris(3,5-dimethylphenylcarbamate).…”

Polysaccharide- and β-Cyclodextrin-Based Chiral Selectors for Enantiomer Resolution: Recent Developments and Applications

“…A combination of chiral liquid chromatography and MS, in an attempt to increase the selective and sensitive qualification and quantification of ephedrine and pseudoephedrine as illicit drugs ( Supplementary Materials Figure S24 ), has been reported by Karakka Kal et al [ 56 ]. A large set of different chiral columns was used in this study, which are commercially available as Chiralpak ® OD-H, Chiralpak ® OJ-H, Chiralpak ® IC, Lux ® Cellulose-1, Lux ® Cellulose-2, Lux ® i-Cellulose-5 ( Table 1 ), Chiralpak ® AD-H, Chiralpak ® IA, YMC CHIRAL ART Amylose-C, Lux ® Amylose-1, Lux ® i-Amylose-1, and Lux ® Amylose-2 ( Table 2 ).…”

Annual banned‐substance review – Analytical approaches in human sports drug testing

“…Although the extent of performance‐enhancing effects was reported as small as outlined in a recent meta‐analysis that included studies with pseudoephedrine dosages up to 2.8 mg/kg bodyweight, the misuse of even larger doses cannot be excluded and adequate test methods are required . The separation of pseudoephedrine enantiomers is unlikely to be necessary in routine doping controls; nevertheless, an excellent separation employing an analytical column with an i‐amylose stationary phase (4.6 × 150 mm, 5 μm particle size) and n‐hexane containing 0.05% formic acid (solvent A) and 2‐propanol containing 0.05% formic acid (solvent B) was accomplished . Despite the unconventional composition of the mobile phases, compatibility with mass spectrometry was shown, enabling detection limits of 20 ng/mL.…”