Review: Recent Application of Chiral Liquid Chromatography-Tandem Mass Spectrometric Methods for Enantiomeric Pharmaceutical and Biomedical Determinations

Abstract

The technology of analyzing the pharmacological and toxicological properties of chiral drugs has become more commonly utilized since the knowledge of the biological actions of enantiomers has been gradually acquired during the last few decades. This work reviews the applications of chiral liquid chromatography coupled to tandem mass spectrometry (LC-MS) for the analysis of chiral pharmaceuticals since 2005. The enantioselective determinations in pharmaceutical and biomedical fields with LC-MS are classified based on three mobile phase modes, including normal phase, reversed phase and polar organic solvent, in terms of their compatibility with various ionization sources and specific applications.

Chromatographic Studies of Protein-Based Chiral Separations

“…In the late 1970s, Yoshio Okamoto synthesized a helical polymer of triphenylmethyl methacrylate and used this material to develop chromatographic columns that could be used for chiral separations [4]. Since that time, significant effort has been aimed at creating chiral stationary phases (CSPs) that can be used in chromatography for the separation and analysis of chiral compounds [3–9]. …”

“…In addition, the S -enantiomers of barbiturates such as pentobarbital, hexobarbital, and mephobarbital are sedatives/hypnotics while the R -enantiomers tend to be inactive [10,15]. These differences have made it necessary to provide pure enantiomers in pharmaceutical formulations and/or to determine the effects the separate enantiomers may have in the body [7,9]. This, in turn, has led to the need for analytical methods and preparative techniques that can be used to analyze and separate chiral compounds in pharmaceutical samples [7,9].…”

“…These differences have made it necessary to provide pure enantiomers in pharmaceutical formulations and/or to determine the effects the separate enantiomers may have in the body [7,9]. This, in turn, has led to the need for analytical methods and preparative techniques that can be used to analyze and separate chiral compounds in pharmaceutical samples [7,9]. …”

“…These methods have included gas chromatography, thin layer chromatography, high-performance liquid chromatography (HPLC), supercritical fluid chromatography, and capillary electrophoresis [6,9,16–18]. Methods based on HPLC have been of particular interest [6,9,17–19]. Many types of stereoselective binding agents have been used to prepare CSPs for HPLC.…”

Analysis of N ′-nitrosonornicotine enantiomers in human urine by chiral stationary phase liquid chromatography–nanoelectrospray ionization–high resolution tandem mass spectrometry

“…The use of chiral stationary phase LC-NSI-HRMS/MS was critical for the success of this project, as it provided the requisite enantiomer separation, sensitivity, and specificity for clear analysis of the extremely low levels of NNN enantiomers in human urine. While previous studies have described the analysis of urinary enantiomeric metabolites using LC-MS/MS techniques [21, 22], this is apparently the first study to combine chiral stationary phase separations with nanoelectrospray ionization and high resolution MS/MS to quantify trace levels of enantiomeric metabolites in human urine. Furthermore, use of a monitor amine, [pyridine-D 4 ]nornicotine, gave us confidence that artifact formation during analysis was minimal.…”