Jauh T. Lee

Enantiomeric composition of nornicotine, anatabine, and anabasine in tobacco

Literature reports on the optical purity of the minor alkaloids in tobacco leaf and its products often contradict one another. The enantiomeric compositions of nornicotine, anatabine, and anabasine were measured using gas chromatography/mass spectrometry (GC/MS) (with a chiral stationary phase) in three types of tobacco leaf (Burley, Turkish, and Virginia); three types of smokeless tobacco (loose-leaf, dry snuff, and moist snuff); and four types of cigarettes. Regardless of the tobacco type or product, anabasine always had the highest relative percentage of the minor (R)-(+)-enantiomeric component (between 40 and 46% vs. 54–60% of the (S)-(−)-enantiomer). Of the four common tobacco alkaloids, nicotine seems to have the highest enantiomeric excess (e.e.) while anabasine has the lowest (in the tobacco leaf and tobacco products analyzed). Nornicotine and anatabine have intermediate e.e. values. Chirality 11:82–84, 1999.

Separation of enantiomers by capillary electrophoresis using pentosan polysulfate

Pentosan polysulfate, a semisynthetic polysaccharide, was employed as a chiral run buffer additive in capillary electrophoresis. Twenty‐eight racemic analytes were resolved. The separations were successful only at low pH when the analytes were significantly protonated. This suggests that ionic interactions were the dominant associative interactions between the anionic pentosan polysulfate and the positively charged analytes. Compared to other linear, carbohydrate‐based chiral selectors (i.e., chondroitin sulfates, heparin and dextran sulfate) pentosan polysulfate has some characteristics common of anionic polysaccharides; yet it has several differences in its structure and properties which account for its unusual enantioselectivity. The effects of pH, concentration of phosphate buffer, concentration of pentosan polysulfate and the type and concentration of organic modifier on the enantiomeric separations were investigated. The optimization of these separations were dependent on the nature of the analytes and could be achieved by the proper choice of experimental conditions.

Enantiomeric impurities in chiral catalysts, auxiliaries, synthons and resolving agents. Part 2

Abstract The enantiomeric purity of reagents used in asymmetric synthesis is of fundamental importance when evaluating the selectivity of a reaction and the product purity. In this work, 109 chiral reagents (many recently introduced) are assayed. Approximately 64% of these reagents had moderate to high levels of enantiomeric impurities (i.e. from >0.1% to

Reversal of enantiomeric elution order on macrocyclic glycopeptide chiral stationary phases

The macrocyclic glycopeptides, vancomycin, teicoplanin, and ristocetin A are naturally occurring chiral molecules that have been developed into one of the most useful classes of chiral stationary phases (CSPs) for HPLC. Since these chiral selectors are structurally related, they tend to have similar, but not identical, enantioselectivities for most compounds. CSPs, of this type, with opposite enantioselectivities are rare. Two exceptions have been found to this. The oxazolidiones (starting materials for asymmetric synthesis) and dansyl amino acids all show a reversal in enantioselective retention on one of these three related CSPs. By using the HPLC assays developed for these compounds, the levels of enantiomeric impurities can be measured down to ∼0.01%. The enantiomeric purity of commercial oxazolidiones was determined.

Chiral separations of indan, tetralin and benzosuberan derivatives by capillary electrophoresis

Abstract Several indan, tetralin and benzosuberan derivatives of diverse polarities were enantio-resolved by the use of sulfated β-cyclodextrins (CDs) or mixtures of sulfated β-CDs and γ-CD as chiral additives in capillary electrophoresis. Mixtures of sulfated β-CDs and hydroxypropyl β-CDs were also successfully utilized for enantiomeric and diastereomeric separations of some of the tetralin derivatives with two stereogenic centers. Both neutral and anionic analytes were resolved in the reversed electrophoretic polarity mode. Cationic amino derivatives of indan and tetralin were enantio-resolved in the conventional electrophoretic polarity mode.

Effective methodologies for enantiomeric separations of 150 pharmacology and toxicology related 1°, 2°, and 3° amines with core-shell chiral stationary phases

HIGHLIGHTSRapid method development for optimized enantiomeric separations of 150 amines.Biological compatible MS analysis of 150 amines.Complementary separations with macrocyclic chiral selectors.High‐throughput chiral separations with core‐shell chiral stationary phases.Single LC–MS chiral separation of 18 illicit substances in 35min. ABSTRACT Core‐shell particles (superficially porous particles, SPPs) have been proven to provide high‐throughput and effective separations of a variety of chiral molecules. However, due to their limited commercialization, many separations have not been reported with these stationary phases. In this study, four SPP chiral stationary phases (CSPs) were utilized for the enantiomeric separation of 150 chiral amines. These amines encompass a variety of structural and drug classes, which are particularly important to the pharmaceutical industry and in forensics. This comprehensive evaluation demonstrates the power of these CSPs and the ease of method development and optimization. The CSPs used in this study included the macrocyclic glycopeptide‐based CSPs (VancoShell and NicoShell), the cyclodextrin‐based CSP (CDShell‐RSP), and the cyclofructan‐based CSP (LarihcShell‐P). These CSPs offered versatility for a variety of applications and worked in a complementary fashion to baseline separate all 150 amines. The LarihcShell‐P was highly effective for separating primary amines. VancoShell, NicoShell, and CDShell‐RSP were useful for separating all types of amines. These CSPs are multi‐modal and can be utilized with mass spectrometry compatible solvents. Eighteen racemic controlled substances were simultaneously baseline separated in a single liquid chromatography–mass spectrometry (LC–MS) analysis. Details in high‐performance liquid chromatography (HPLC) parameters will be discussed as well as the improved chromatographic performance afforded by the SPP CSPs.

A comprehensive methodology for the chiral separation of 40 tobacco alkaloids and their carcinogenic E/Z-(R,S)-tobacco-specific nitrosamine metabolites

The predominant enantiomer of nicotine found in nature is (S)-nicotine and its pharmacology has been widely established. However, pharmacologic information concerning individual enantiomers of nicotine-related compounds is limited. Recently, a modified macrocyclic glycopeptide chiral selector was found to be highly stereoselective for most tobacco alkaloids and metabolites. This study examines the semi-synthetic and native known macrocyclic glycopeptides for chiral recognition, separation, and characterization of the largest group of nicotine-related compounds ever reported (tobacco alkaloids, nicotine metabolites and derivatives, and tobacco-specific nitrosamines). The enantioseparation of nicotine is accomplished in less than 20s for example. All liquid chromatography separations are mass spectrometry compatible for the tobacco alkaloids, as well as their metabolites. Ring-closed, cyclized structures were identified and separated from their ring-open, straight chain equilibrium structures. Also, E/Z-tobacco-specific nitrosamines and their enantiomers were directly separated. E/Z isomers also are known to have different physical and chemical properties and biological activities. This study provides optimal separation conditions for the analysis of nicotine-related isomers, which in the past have been reported to be ineffectively separated which can result in inaccurate results. The methodology of this study could be applied to cancer studies, and lead to more information about the role of these isomers in other diseases and as treatment for diseases.

Chromatographic separation of racemic praziquantel and its residual determination in perch by LC-MS/MS

An enantioselective depletion study of praziquantel (PZQ) in perch muscle was done using a simple, sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Two cyclic polypeptides and two cyclic saccharide chromatographic columns were evaluated. The new hydroxypropyl β-cyclodextrin (HP-RSP) superficially porous particle (SPP) column produced the optimum separation and was selected for the study. Deuterium labeled PZQ-d11 was used as the internal standard. The method was linear over concentration ranges of 5.00-5.00×102μgL-1 (r2≥0.99) for (-)-R-PZQ and (+)-S-PZQ. The average recoveries of R-PZQ and S-PZQ at three spiked levels of 5.00, 50.00 and 5.00×102μgkg-1 ranged from 86.1% to 98.2%, and the intra-day and inter-day relative standard deviations were less than 5%. The decision limit (CCα) and detection capability (CCβ) of R-PZQ and S-PZQ in perch muscle matrices were all 1.0μgkg-1 and 5.0μgkg-1, respectively. The method was successfully applied in monitoring the depletion of praziquantel enantiomers in perch muscle following oral administration. The elimination rate of R-PZQ and S-PZQ in perch muscle tissue is equivalent.

Mass Spectrometry-Compatible Enantiomeric Separations of 100 Pesticides Using Core–Shell Chiral Stationary Phases and Evaluation of Iterative Curve Fitting Models for Overlapping Peaks

Pesticides are often chiral, and their isomers have different activity, toxicity, metabolism, and degradation properties. Perhaps, the most complex are the synthetic pyrethroid insecticides that have up to 8 stereoisomers, but not all are active. Pyrethroids are toxic to aquatic invertebrates and non-targeted species like honey bees since they persist in the environment. Extensive biological studies of the pyrethroid enantiomers are limited. Possibly, this is because liquid chromatography enantiomeric methods for these studies often have limitations with mass spectrometry (MS) compatibility. In this study, an effective methodology was developed with MS compatible solvents to evaluate several core–shell (superficially porous particle, SPP) chiral stationary phases (CSPs) for the enantiomeric separation of several classes of chiral pesticides. The CSP with the broadest selectivity or spectrum amongst all pesticide classes was the hydroxypropyl-β-cyclodextrin. The other CSPs (cyclofructan, macrocyclic glycopeptide, and quinine-based selectors) had more selective applications including separations of the pesticides with amine or acid functionalities. Overall, 74 of 100 pesticides were baseline-separated. Most of the remaining ones had multiple stereogenic centers and had only one overlapping pair. Such cases were evaluated with a convenient peak area extraction protocol by iterative curve fitting. This approach will lead to more facile enantiomeric analyses where MS is needed to overcome complex matrices and reduce extensive method optimization.Graphical abstract