Gas chromatographic determination of enantiomers as diastereomers following pre‐column derivatization and applications to pharmacokinetic studies: A review

Abstract

The introduction of chiral chromatographic methods has revolutionized the art of separation and quantitation of chiral drugs in biological fluids. A large number of chiral derivatization reagents for various functional groups are available commercially. Therefore, pre-column derivatization methods have become attractive and simple for the gas chromatographic assays in biological fluids. The intent of this article is to review the pre-column chiral derivatization reagents employed in gas chromatographic separations and analyses of enantiomers. A discussion of numerous procedures necessary to develop a quantitative gas chromatographic assay method for drug enantiomers is presented. In this regard, quantitative gas chromatographic assays based on this approach have been applied to investigate the stereoselective pharmacokinetics of several chiral drugs such as fenfluramine, norfenfluramine, methylphenidate, etodolac, propranolol, suprofen and methoxyphenamine.

Chiral separation by chromatographic and electromigration techniques. A Review

“…A survey of chiral derivatization reagents for GC and their application to various compound classes including applications to pharmacokinetic studies is given by Srinivas et al [271].…”

“…Most frequently used chiral derivatization reagents in GC are S(À) heptafluorobutyryl prolyl chloride, (À) menthyl chloroformate, Sa-methoxy-a-trifluoromethylphenyl acetyl chloride, S(À)-trifluoroacetyl prolyl chloride and R-(À)-2,2,2-trifluoro-1-(9-anthryl) ethanol [271]. More recently applied derivatization reagents are isopinocampheylamine [272] and O,O 0 -(R,R)-diacylated tartaric acid anhydrides [273].…”

“…Examples for the use of GC for chiral separation of drugs following pre-column derivatization for pharmacokinetic studies were given by Srinivas et al [271].…”

The Cold Contact Method as a Simple Drug Interaction Detection System

“…A survey of the literature reveals that there are very few reported methods for the determination of ETD in biological fluids, pharmaceutical formulations and in presence of its enantiomer. Of those studies reported, the techniques used include chromatography, HPLC [2][3][4][5], GC [6][7][8], in addition to spectrofluorimetric [9] and spectrophotometric methods [9][10][11]. However, an extensive survey of the literature revealed that there is no method available for the simultaneous determination of ETD in pure form and pharmaceutical formulations by oxidation-reduction reactions.…”

Determination of Enantiomeric Composition of Substituted Tetrahydroisoquinolines Based on Derivatization with Menthyl Chloroformate

“…These methods typically employ gas chromatography coupled to mass spectrometry [10,11] and liquid chromatography with UV [12,13], fluorescent [14] or mass-spectrometric detection [15,16]. In cases when an achiral GC or LC column is used for the determination of enantiomeric excess, the mixture of enantiomers needs to be reacted with optically pure reagents prior to the analysis [17,18]. There are a number of agents available for pre-column derivatization, such as Mosher's acid [19][20][21], camphanic acid [22], perfluoro-2-propoxypropionylchloride [11] and others.…”