Enantiospecific analysis: Applications in bioanalysis and metabolism

Abstract

Enantiospecific analysis has a significant role in modern drug development from discovery-chemistry to the clinical evaluation of novel compounds. Chromatographic techniques, involving the use of either chiral derivatizing agents or chiral stationary phases, represent the most commonly used approaches to enantiospecific analysis. The advantages and limitations of these two techniques are examined using the analysis of the enantiomers of the 2-arylpropionic acids (tiaprofenic acid and ibuprofen) and the chiral N-oxides of N-ethyl-N-methylaniline and pargyline, as representative examples for each approach. The potential of biosensors in enantiospecific analysis is addressed and some preliminary results on the development of an enantioselective biosensor for the analysis of (S)-warfarin are presented.

Enantiospecific analysis of ibuprofen by high performance liquid chromatography: Determination of free and total drug enantiomer concentrations in serum and urine

“…The assay was further validated by analysing a series of samples "spiked" with mixtures of the individual enantiomers at three concentration levels. This validation approach is necessary as biological samples from pharmacokinetic and metabolic studies will contain non-racemic mixtures of enantiomers due to stereoselectivity in drug metabolism and disposition [42]. The precision and accuracy values calculated for these analyses are shown in Table II.…”

“…The main advantage of using direct methods involving chiral stationary phases (CSPs) is that derivatization is usually not required. Direct separation of drug enantiomers in biological fluids using CSPs frequently shows good selectivity between enantiomers but the chromatographic conditions tend to be fairly restricted and the presence of co-extracted endogenous contami-nants and/or trace impurities may have marked effects on resolution and column stability [41,42]. Separation of ibuprofen enantiomers in plasma on an (xl-acid glycoprotein CSP, using both isocratic and gradient elution, has been reported [15][16][17] but poor sensitivity and batch to batch variability in the stationary phases may limit the utility of the method.…”

Enantiospecific analysis by capillary electrophoresis: Applications in drug metabolism and pharmacokinetics

“…However, chromatographic analysis time was relatively long (ca. 80 min) and the enantiomeric resolution incomplete, such that minor quantities of the second eluting enantiomer (the (±)-isomer) could not be accurately determined [96,98].…”

Chiral bioanalysis of torcetrapib enantiomers in hamster plasma by normal-phase liquid chromatography and detection by atmospheric pressure chemical ionization tandem mass spectrometry

“…It is therefore important to develop enantioselective separation methods for studies on stereoselective pharmacokinetics and metabolism [6]. Typically enantiomers can be separated using different approaches, viz., formation of diastereomers prior to separation on non-chiral column or addition of chiral additives to form diastereomeric complexes followed by separation on a non-chiral column or direct separation on a chiral column [7,8]. Lee et al [9] have described the distribution of TTB in human plasma and different lipoprotein components of human plasma by GC-MS/MS.…”