title: Simultaneous identification of the enantiomers and diastereomers of N,O-di-trifluoroacetylated ephedrine and norephedrine in blood plasma using chiral capillary gas chromatography-mass spectrometry with selected ion monitoring.
abstract: A method for identifying the enantiomers of N,O-di-trifluoroacetylated ephedrine (EP) and norephedrine (NE) and the enantiomers of pseudoephedrine (PEP) and pseudonorephedrine (PNE) in plasma was developed using chiral capillary gas chromatography-mass spectrometry (GC-MS) with selected ion monitoring (SIM). N,O-Di-trifluoroacethyl (TFA) derivatization was accomplished in a dried hydrochloride extract of plasma (minimum quantity of 0.2 mL). An SIM GC-MS method with a β-cyclodextrin chiral capillary column allowed the successful and simultaneous detection of each TFA-derivatized stereoisomer of EP, NE, PEP, PNE, and an internal standard (IS; S-(+)-ethylamphetamine). Each TFA-drivatized stereoisomer was identified using four mass fragment ions (m/z 140, 154, 168, and 230). The TFA-derivatized stereoisomers of EP, NE, PEP, PNE, and IS were separated completely and were detected with sufficient sensitivity. The assay allowed the stereoisomers to be determined in a linear range of 12.5-1250 ng/mL for the EP stereoisomers and a linear range of 5-1250 ng/mL for the PEP, NE, and PNE stereoisomers. The detection limits were 7.5 ng/mL for the EP stereoisomers and 2.5 ng/mL for the PEP, NE, and PNE stereoisomers. The intra- and interday precisions were less than 5.9% and 8.2%, respectively. This chiral capillary SIM GC-MS method was sufficiently effective in the analysis of plasma from users of over-the-counter cold medicines and was also fully applicable to the plasma analysis of guinea pigs following their treatment with racemic EP.
authors.affiliation: Department of Legal Medicine, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan. tnagai@dokkyomed.ac.jp
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Nagai
authors.forename: Akira
authors.initials: A
authors.lastname: Kurosu
authors.forename: Kazumi
authors.initials: K
authors.lastname: Matsushima
authors.forename: Junko
authors.initials: J
authors.lastname: Maeda
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tohei
authors.forename: Shinobu
authors.initials: S
authors.lastname: Yamauchi
authors.forename: Masahito
authors.initials: M
authors.lastname: Hitosugi
authors.forename: Shogo
authors.initials: S
authors.lastname: Tokudome
mesh_terms: D000662:Amphetamines / Q000097:blood; D000818:Animals; D002138:Calibration; D004809:Ephedrine / Q000097:blood* / Q000302:isolation & purification*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D010665:Phenylpropanolamine / Q000097:blood* / Q000302:isolation & purification*; D010949:Plasma / Q000737:chemistry; D054199:Pseudoephedrine / Q000097:blood; D013237:Stereoisomerism; D047392:beta-Cyclodextrins / Q000097:blood
chemical_list: D000662:Amphetamines; D047392:beta-Cyclodextrins; C016434:ethylamphetamine; C005331:norpseudoephedrine; D010665:Phenylpropanolamine; D054199:Pseudoephedrine; D004809:Ephedrine