Chiral separations in normal phase liquid chromatography: Enantioselectivity of recently commercialized polysaccharide-based selectors. Part I: Enantioselectivity under generic screening conditions
ABSTRACT Four recently commercialized polysaccharide-based chiral stationary phases, Sepapak(®) 1, Sepapak(®) 2, Sepapak(®) 3, and Sepapak(®) 4, now called Lux(®) Cellulose-1, Lux(®) Cellulose-2, Lux(®) Amylose-2 and Lux(®) Cellulose-4, respectively, were examined for their enantioselectivity on a set of 61 racemic compounds by applying the screening conditions of a previously developed chiral screening strategy in normal phase liquid chromatography (NPLC) [N. Matthijs et al., J. Chromatogr. A 1041 (2004) 119-133]. The enantioselectivity on these phases was compared to that on the initial set of polysaccharide-based phases, Chiralpak(®) AD-H, Chiralcel(®) OD-H, and Chiralcel(®) OJ-H, used in the earlier defined strategy. The results showed that 53 compounds out of 61 (86.9%) were resolved on the initial set of chiral stationary phases (CSPs) using two mobile phases per compound, either heptane-ethanol-diethylamine (DEA) or heptane-isopropanol-DEA for testing basic compounds and heptane-ethanol-trifluoroacetic acid (TFA) or heptane-isopropanol-TFA for acidic, bifunctional and neutral compounds. The recently commercialized set of columns gave 54 separations in total (88.5%). Our results indicated that ethanol (EtOH) as polar modifier provides a higher success rate and better resolutions than isopropanol (IPA) on both sets of stationary phases. However, the usefulness of the mobile phase with IPA as polar modifier cannot be neglected for complementarity reasons. It was found that the screening is improved by the introduction of the recently commercialized polysaccharides based CSPs since they provided enantioseparation for compounds that were not resolved by the traditional CSPs. The combination between the initial and the recently commercialized CSPs showed enantioresolution for 55 compounds out of 61 (90%), among which 47 were baseline resolved.
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- "The decisions made for these CPPs were based on literature and screening steps. The data corroborated from Younes et al.  that showed the same effect between ethanol and isopropanol with the results published by Ates et al.  showing comparable cumulative success rates for both mobile phases compared (i.e. acetonitrile versus methanol) were the basis for the screening step. "
ABSTRACT: This paper focuses on implementing a design space approach and on the critical process parameters (CPPs) to consider when applying the Quality by Design (QbD) concepts outlined in ICH Q8(R2), Q9 and Q10 to analytical method development and optimization for three chiral compounds developed as modulators of small conductance calcium-activated potassium (SK) channels. In this sense, an HPLC method using a polysaccharide-based stationary phase containing a cellulose tris (4-chloro-3-methylphenylcarbamate) chiral selector in polar organic solvent chromatography mode was considered. The effects of trifluoroacetic acid (TFA) and n-hexane concentration in an acetonitrile (MeCN) mobile phase were investigated under a wide range of column temperatures. Good correlations were found between the observed data obtained after using a central composite design and the expected chromatographic behaviours predicted by applying the design of experiments-design space (DoE-DS) methodology. The critical quality attribute represented here by the separation criterion (S(crit)) allowed assessing the quality of the enantioseparation. Baseline separation for the compounds of interest in an analysis time of less than 20min was possible due to the original and powerful tools applied which facilitated an enhanced method comprehension. Finally, the advantage of the DoE-DS approach resides in granting the possibility to concurrently assess robustness and identify the optimal conditions which are compound dependent.Journal of pharmaceutical and biomedical analysis 02/2013; 74:273-83. DOI:10.1016/j.jpba.2012.10.015 · 2.83 Impact Factor
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ABSTRACT: A strategy aimed at developing faster chiral screening approaches is proposed in this paper by mixing samples and simultaneously screening the resulting mixture of racemates. The data matrix of the mixture obtained by diode array detector or mass spectrometry is deconvoluted into resolved chromatograms and spectra through a multivariate curve resolution–alternating least squares algorithm. The individual racemates are then identified through the resolved UV spectra, and enantiomeric excess ratios can be measured via the resolved chromatograms. Two representative experiments were carried out to verify the feasibility of the strategy. A mixture containing five pairs of racemic solutes was successfully screened on Chiralcel OD column in one-fifth of the conventional analysis time. Another mixture containing 10 racemates gained nine-tenths of the original screening time on three CSPs with a predictive accuracy above 90 %.Chromatographia 09/2013; 76(17-18). DOI:10.1007/s10337-013-2520-9 · 1.37 Impact Factor
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ABSTRACT: Enantiomers (stereoisomers) can exhibit substantially different properties if present in chiral environments. Since chirality is a basic property of nature, the different behaviors of the individual enantiomers must be carefully studied and properly treated. Therefore, enantioselective separations are a very important part of separation science. To achieve the separation of enantiomers, an enantioselective environment must be created by the addition of a chiral selector to the separation system. Many chiral selectors have been designed and used in various fields, such as the analyses of drugs, food constituents and agrochemicals. The most popular have become the chiral selectors and/or chiral stationary phases that are of general use, i.e., are applicable in various separation systems and allow for chiral separation of structurally different compounds. This review covers the most important chiral selectors / chiral stationary phases described and applied in high performance liquid chromatography and capillary electrophoresis during the period of the last three years (2008–2011).Central European Journal of Chemistry 06/2012; 10(3). DOI:10.2478/s11532-011-0142-3 · 1.33 Impact Factor