Enantiomeric separations of illicit drugs and controlled substances using cyclofructan‐based (LARIHC) and cyclobond I 2000 RSP HPLC chiral stationary phases

Abstract

Recently a novel class of chiral stationary phases (CSPs) based on cyclofructan (CF) has been developed. Cyclofructans are cyclic oligosaccharides that possess a crown ether core and pendent fructofuranose moieties. Herein, we evaluate the applicability of these novel CSPs for the enantiomeric separation of chiral illicit drugs and controlled substances directly without any derivatization. A set of 20 racemic compounds were used to evaluate these columns including 8 primary amines, 5 secondary amines, and 7 tertiary amines. Of the new cyclofructan based LARIHC columns, 14 enantiomeric separations were obtained including seven baseline and seven partial separations. The LARIHC CF6-P column proved to be the most useful in separating illicit drugs and controlled substances accounting for 11 of the 14 optimized separations. The polar organic mode containing small amounts of methanol in acetonitrile was the most useful solvent system for the LARIHC CF6-P CSP. Furthermore, the LARIHC CF7-DMP CSP proved to be valuable for the separation of the tested chiral drugs resulting in four of the optimized enantiomeric separations, whereas the CF6-RN did not yield any optimum separations. The broad selectivity of the LARIHC CF7-DMP CSP is evident as it separated primary, secondary and tertiary amine containing chiral drugs. The compounds that were partially or un-separated using the cyclofructan based columns were screened with a Cyclobond I 2000 RSP column. This CSP provided three baseline and six partial separations.

Separation of therapeutic peptides with cyclofructan and glycopeptide based columns in hydrophilic interaction liquid chromatography

“…Their different functionalities are summarized in Fig. S1 and include native cyclofructan 6 (CF6) (Frulic TM N) [27][28][29], an isopropyl carbamate modified cyclofructan 6 stationary phase (Larihc TM CF6-P) found to be excellent for chiral [30] as well as HILIC separations [31], and a 4-chloromethyl-styrene-divinylbenzene resin based CF6 column [32,33].…”

Chiral and stable isotope analysis of synthetic cathinones

“…However, only four out of the fourteen enantiomeric pairs were baseline separated (R s = 1.78, 1.84, 1.84 and 1.86), suggesting further investigation may be required. Other phases such as isopropyl-carbamate cyclofructan 6 (Larihc CF6-P) and vancomycin-based macrocyclic glycopeptide (Chirobiotic V2) were used for chiral separation of cathinone [45,46] and methcathinone [45]. Although reasonable resolutions were achieved and individual enantiomers were quantified, further investigation is required for baseline separation and chiral separation of other novel synthetic cathinones.…”

Simultaneous chiral analysis of amphetamine‐type stimulants and ephedrine by capillary electrophoresis coupled to time‐of‐flight mass spectrometry

“…One enantiomer of a particular drug can be accepted for its medicinal usage, while the other enantiomer may be a drug of abuse . For example, (R)‐(−)‐MA can be a nasal decongestant while (S)‐(+)‐MA is a main smuggled drug on the drug market …”

“…Nuclear magnetic resonance spectroscopy can provide chiral information of enantiomers by adding the chiral solvating agent before detecting, while it usually needs to combine other methods (such as GC‐MS) to identify an unknown seized mixture . For both GC and HPLC techniques, a prederivatization step or a specific chiral column is necessary for successful separation . Compared with GC‐MS and HPLC‐MS, CE has an advantage on small solvent and sample consumption .…”