“…Enantiomers of drugs may also differ in the rate of their metabolism. For example, the stereoselective metabolism of amphetamine, − methamphetamine, , and ephedrine , has been described in the literature. Increased interest in stereochemical aspects of pharmacological activity and drug disposition has led to the need for development of new sensitive and specific methods for the detection of enantiomers in biological fluids. 1 Chemical structure and absolute configuration of the compounds studied.…”
mentioning
confidence: 99%
“…A number of procedures have been reported for the determination of enantiomers of these compounds, including high-performance liquid chromatography (HPLC) − and gas chromatography (GC). Separation of the enantiomers by GC has been achieved either by using an optical active stationary phase − or by reacting the enantiomers with a suitable asymmetric reagent. ,, The published methods for quantification of enantiomers by GC are not adequate for the determination of trace amounts of enantiomers containing more than one reactive functional group, e.g., hydroxymaines, and especially for the simultaneous quantification of metabolites with similar structures, because of their insufficient resolution and sensitivity or the temperature limitations of certain columns. Donike − has described the selective N-trifluoroacylation−O-trimethylsilylation of phenol alkylamines and hydroxyamines as well as their corresponding hydrochlorides.…”
The enantiomers of amphetamines, phenol alkylamines, and hydroxyamines are separated by using α-methoxy-α-(trifluoromethyl)phenylacetyl chloride as the chiral derivatizing agent for amino groups. Prior to N-acylation, amine salts are converted into the free bases and hydroxyl groups into O-silyl ethers by reaction with N-methyl-N-silylamides. N-Methyl-N-(trimethylsilyl)trifluoroacetamide, N-methyl-N-(triethylsilyl)trifluoroacetamide, or N-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide was used to protect the hydroxyl groups by TMS, TES, or the tBDMS groups. All these N-methyl-N-silylamides were able to convert amino salts to the free bases. The reaction is selective and rapid, and the diastereomeric derivatives are well separated by capillary gas-liquid chromatography. This procedure is suitable for simultaneous determination by gas chromatography/mass spectrometry with selected-ion monitoring and is also applicable to quantification of the compounds in a biological matrix.
“…Enantiomers of drugs may also differ in the rate of their metabolism. For example, the stereoselective metabolism of amphetamine, − methamphetamine, , and ephedrine , has been described in the literature. Increased interest in stereochemical aspects of pharmacological activity and drug disposition has led to the need for development of new sensitive and specific methods for the detection of enantiomers in biological fluids. 1 Chemical structure and absolute configuration of the compounds studied.…”
mentioning
confidence: 99%
“…A number of procedures have been reported for the determination of enantiomers of these compounds, including high-performance liquid chromatography (HPLC) − and gas chromatography (GC). Separation of the enantiomers by GC has been achieved either by using an optical active stationary phase − or by reacting the enantiomers with a suitable asymmetric reagent. ,, The published methods for quantification of enantiomers by GC are not adequate for the determination of trace amounts of enantiomers containing more than one reactive functional group, e.g., hydroxymaines, and especially for the simultaneous quantification of metabolites with similar structures, because of their insufficient resolution and sensitivity or the temperature limitations of certain columns. Donike − has described the selective N-trifluoroacylation−O-trimethylsilylation of phenol alkylamines and hydroxyamines as well as their corresponding hydrochlorides.…”
The enantiomers of amphetamines, phenol alkylamines, and hydroxyamines are separated by using α-methoxy-α-(trifluoromethyl)phenylacetyl chloride as the chiral derivatizing agent for amino groups. Prior to N-acylation, amine salts are converted into the free bases and hydroxyl groups into O-silyl ethers by reaction with N-methyl-N-silylamides. N-Methyl-N-(trimethylsilyl)trifluoroacetamide, N-methyl-N-(triethylsilyl)trifluoroacetamide, or N-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide was used to protect the hydroxyl groups by TMS, TES, or the tBDMS groups. All these N-methyl-N-silylamides were able to convert amino salts to the free bases. The reaction is selective and rapid, and the diastereomeric derivatives are well separated by capillary gas-liquid chromatography. This procedure is suitable for simultaneous determination by gas chromatography/mass spectrometry with selected-ion monitoring and is also applicable to quantification of the compounds in a biological matrix.
“…Dale et al 34 described the synthesis of optically active α‐methoxy‐α‐trifluoromethylphenylacetic acid (Mosher's reagent) and its application to the determination of the enantiomeric purity of amines and alcohols by 1 H and 19 F nuclear magnetic resonance (NMR). Nichols et al 35 and Gal36, 37 extended the use of Mosher's reagent to GC determination of the enantiomeric purity of chiral amines. Since Mosher's reagent is highly resistant to racemization due to the lack of α‐hydrogen and the acid chloride (α‐methoxy‐α‐trifluoromethylphenylacetyl chloride: MTPA‐Cl) is commercially available in its resolved form with high enantiomeric purity, we chose MTPA‐Cl as the chiral reagent for separation of DL ‐serine.…”
D-Serine is a co-agonist of the N-methyl-D-aspartate receptor in glutamate neurotransmission and has been proposed as a potential therapeutic agent for schizophrenia. However, D-serine also acts as a nephrotoxic substance in rats at high doses. To investigate the pharmacokinetics and toxicokinetics of D-serine, a method for the stereoselective determination of serine enantiomers in rat plasma was developed using GC-MS with selected ion monitoring (GC-MS-SIM). DL-[(2)H(3)]Serine was used as an internal standard to account for losses associated with the extraction, derivatization and chromatography. Serine enantiomers were purified by cation-exchange chromatography using BondElut SCX cartridge and derivatized with HCl in methanol to form methyl ester followed by subsequent N,O-diacylation with optically active (+)-α-methoxy-α-trifluoromethylphenylacetyl chloride to form epimeric amide. Quantitation was performed by SIM of the molecular-related ions of the epimers in the chemical ionization mode. The intra- and inter-day reproducibility of the assay was less than 5% for D-serine and 3% for L-serine. The method was successively applied to study the pharmacokinetics of D-serine in rats.
“…At higher doses, (S)‐(+)‐amphetamine has stimulant properties that are stronger than R‐(−)‐amphetamine, and increases dopamine activity. Hence, (S)‐(+)‐amphetamine is several times more potent than the R‐(−)‐enantiomer in eliciting central nervous system effects . Also, the R‐(−)‐amphetamine produces more cardiovascular and peripheral effects than the (S)‐(+)‐amphetamine .…”
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.
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