Separation of the enantiomers of primary and secondary amphetamines by liquid chromatography after derivatization with (−)-1-(9-fluorenyl)ethyl chloroformate

Abstract

The chiral reagent (-)-l-(9-fluorenyl)ethyl chloroformate (FLEC) has been evaluated for the enantioselective analysis of amphetamines by liquid chromatography. For separation of the FLEC cliastereomers conventional reversed-phase conditions were used. The conditions affording the best enantiomeric resolution and sensitivity were determined for amphetamine, methamphetamine, ephedrine, pseucloephedrine, 3,4-methyleneclioxyamphetamine (MDA), 3,4methyleneclioxymethamphetamine (MDMA), and 3,4-methyleneclioxyethylamphetamine (MDE). All the amphetamines assayed could be separated with resolution factors ranging from 0.91 to 1.92.Although FLEC is typically used as a fluorogenic reagent, itwas shown that UV cletection is the best option for stereospecific analysis of the methyleneclioxylatd amphetamine derivatives (MDA, MDMA, and MDE), because different fluorimetric responses were obtained for the corresponding cliastereomers. The utility of the proposed conditions for stereoselective analysis of amphetamines in different types of sample is discussed.

Simultaneous chiral separation of methylamphetamine and common precursors using gas chromatography/mass spectrometry

“…Although each of these methods demonstrated baseline separation of the GC peaks from the methylamphetamine enantiomers, all three suffered from lengthy, complicated derivatization procedures. The use of chiral derivatizing reagents for the enantioseparation of methylamphetamine with liquid chromatography (LC) has also been reported and include 2,3,4,6‐tetra‐ O ‐acetyl‐β‐ D ‐glucopyranosyl isothiocyanate,11 (1 S ,2 S ) N ‐[(2‐isothiocyanato)‐cyclohexyl]‐pivalinoyl amide,12 N ‐α‐(2,4‐dinitro‐5‐fluorophenyl)‐ L ‐alaninamide (Marfey's reagent)13 and L ‐(9‐fluorenyl)ethyl chloroformate;14 however, none of these methods were able to achieve baseline separation of the enantiomers of methylamphetamine. Overall, despite the drawbacks already discussed, the combination of L ‐TPC derivatization with achiral GC/MS remains the most widely used 6, 15…”

Chemical Reagents and Derivatization Procedures in Drug Analysis

“…(135) The enantiomeric separation of (−)-1-(9-fluorenyl)ethyl chloroformate chiral derivatives of primary and secondary amphetamines was possible either by UV or fluorescence detection with resolution ranging from 0.9 to about 2. (136) The cardiotonic drug heptaminol has been derivatized with aminoazobenzene-4-isothiocyanate for UV detection at 420 nm (137) or OPA for electrochemical detection. (138) Secondary amines, such as piperazines, were converted into UV derivatives with mtoluoylacyl chloride.…”

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

“…There have been reports on a variety of analytical methodologies for separating enantiomers of illicit drugs and controlled substances, including gas chromatography (GC), high performance liquid chromatography (HPLC), capillary electrophoresis (CE), GC‐MS, LC‐MS, and CE‐ESI‐MS . One approach may be superior to another depending on the goal of the investigator and the nature of the problems to be solved.…”

“…There have been reports on a variety of analytical methodologies for separating enantiomers of illicit drugs and controlled substances, including gas chromatography (GC), [1,[19][20][21] high performance liquid chromatography (HPLC), [1,[22][23][24][25][26][27][28] capillary electrophoresis (CE), [14,29] GC-MS, [30][31][32] LC-MS, [33][34][35][36] and CE-ESI-MS. [37] One approach may be superior to another depending on the goal of the investigator and the nature of the problems to be solved. Clearly, one method may be useful for biological assays while another approach is better suited for forensic assays or quality control of pharmaceutical products.…”