Chiral determination of amphetamine and related compounds using chloroformates for derivatization and high-performance liquid chromatography

Abstract

The enantiomeric determination of amphetamine and various amphetamine-type compounds by liquid chromatography after chiral derivatization with 9-fluorenylmethyl chloroformate-L-proline (FMOC-L-Pro) is reported. The results obtained were compared with those achieved after achiral derivatization with 9-fluorenylmethyl chloroformate and subsequent separation of the derivatives on a beta-cyclodextrin chiral stationary phase. Conditions for the derivatization of amphetamines with FMOC-L-Pro were investigated, including the effect of the derivatization reagent concentration, pH and reaction time, using amphetamine, ephedrine and pseudoephedrine as model compounds. On the basis of these studies, possible conditions for the determination of each amphetamine are indicated. To demonstrate the utility of the proposed procedures, data on linearity, repeatability and sensitivity are given. Results of the determination of ephedrine enantiomers in different pharmaceutical samples are also presented.

Chiral analysis of amphetamine‐type stimulants using reversed‐polarity capillary electrophoresis/positive ion electrospray ionization tandem mass spectrometry

“…GC(-MS) and HPLC(-MS) have been used for the separation of optical isomers of phenethylamines [2][3][4][5][6][7]. There are some limitations of GC and HPLC for simultaneous chiral analysis of ATS.…”

Determination of methamphetamine and amphetamine in abusers' plasma and hair samples with HPLC‐FL

“…In hair samples, AP and MP could also be detected in very low concentrations. al., , Jonsson et al, 1996Herraez-Hernandez et al, 1998), in addition to plasma (Cheung et al, 1997;Nakashima et al, 1990;Nagasawa et al, 1996;Gjerde et al, 1993;Hara et al, 1997;Bogusz et al, 1997) and hair (Nakahara et al, 1993;Slawson et al, 1996;Takayama et al, 1997), have been detailed.Recently, we reported highly sensitive HPLC methods with fluorescence (FL) detection for the determination of AP and MP in urine (Al-Dirbashi et al, 1998a,b, 2000a and hair samples (Al-Dirbashi et al, 1999, 2000b obtained from MP abusers. In these methods, AP and MP were determined after their derivatization with the fluorescent reagent, 4-(4,5-diphenyl-1H-imidazole-2-yl)benzoyl chloride (DIB-Cl) (Nakashima et al, 1995).…”

Chiral derivatization reagents for drug enantioseparation by high‐performance liquid chromatography based upon pre‐column derivatization and formation of diastereomers: enantioselectivity and related structure

“…Reagents such as FMOC-L-Pro (37) and FMOC-L-Phe (38), in which fluorene moiety is chemically bonded to a chiral amino acid, have been used as CDRs for the resolution of enantiomeric amines (Herraez-Hernandez et al, 1998) or polymeric derivatization reagents for the separation of enantiomeric amines and aminoalcoholes (Chou et al, 1989). It was pointed out that the FMOC-L-Pro method combines the high sensitivity provided by chloroformates with the possibility of resolving the isomers of secondary amphetamines, and that the reagent FMOC-L-Pro should be superior to the reagent (À)-MCF because its bulky and rigid fluorenyl group should produce better enantioselectivity and detectability (Herraez-Hernandez et al, 1998). For the polymeric derivatization reagents, several chromatographic conditions have been tried to separate the FMOC-L-Phe diastereomers of D,L-methyl benzylamine and other amines, but most were unsuccessful.…”