Chiral separations in polar organic solvent chromatography: Updating a screening strategy with new chlorine-containing 14 polysaccharide-based selectors

Department of Analytical Chemistry and Pharmaceutical Technology, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium.
Journal of Chromatography B (Impact Factor: 2.73). 09/2008; 875(1):57-64. DOI: 10.1016/j.jchromb.2008.07.038
Source: PubMed


The screening conditions of an existing column and mobile phase selection strategy for chiral drug substances in polar organic solvent liquid chromatography (POSC) were tested for their applicability on two new chlorine-containing polysaccharide-based stationary phases. The selectors of these phases are cellulose tris(3-chloro-4-methylphenylcarbamate) and amylose tris(5-chloro-2-methylphenylcarbamate). The enantioselectivity of these phases is compared to that of the four phases (Chiralpak AD-RH, Chiralcel OD-RH, Chiralpak AS-RH and Chiralcel OJ-RH) used in the earlier defined strategy. A test set of 62 structurally diverse chiral drug substances is analyzed using the screening conditions of the strategy on the six phases. The results confirm that the acetonitrile-based mobile phase provides a higher success rate and better resolutions than the methanol-based also on the new phases. However, the importance of the methanol-based mobile phase cannot be neglected for complementarity reasons; the two mobile phases insure enantioselectivity for different compounds. A third (ethanol-based) mobile phase, not part of the strategy, was also used to screen the two new phases. The joint results led to different possibilities to upgrade the current screening strategy so that improved success rates are obtained. The chlorine-containing chiral stationary phases demonstrated to have an added value to the screening process since they provided enantioresolution for compounds not resolved by non-chlorine-containing ones.

19 Reads
  • Source
    • "These three factors presented in Table 1 were studied across the experimental domain mapped out by the DoE. Additives are typically incorporated into the mobile phases to minimize peak distortion arising from unwanted interactions between polar solutes and the stationary phase, and therefore to sharpen tailing peaks and to increase resolution of chiral compounds [6] [7] [14]. "
    [Show abstract] [Hide abstract]
    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 · 2.98 Impact Factor
  • Source
    • "They are prescribed worldwide as racemic mixtures and are normally monitored in the environment using achiral analytical methods (Madureira et al., 2009, 2010; Alder et al., 2010; Aranas et al., 2011; Lee et al., 2007). There are several publications concerning the enantiomeric separations of this kind of compounds in many types of CSPs; however the majority of them are screening studies of the CSPs (Perrin et al., 2002a, b; Andersson et al., 2003; Ates et al., 2008; Ali et al., 2009a,b). Some studies report changes in EF during wastewater treatment processes (Fono and Sedlak, 2005; Fono et al., 2006; Nikolai et al., 2006; MacLeod et al., 2007; MacLeod and Wong, 2010), demonstrating the potential of chiral beta-blockers to be used as indicators of biologically-mediated transformation or degradation processes as well as effectiveness of WWTP (Hashim et al., 2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Biodegradation of chiral pharmaceuticals in the environment can be enantioselective. Thus quantification of enantiomeric fractions during the biodegradation process is crucial for assessing the fate of chiral pollutants. This work presents the biodegradation of alprenolol and propranolol using an activated sludge inoculum, monitored by a validated enantioselective HPLC method with fluorescence detection. The enantioseparation was optimized using a vancomycin-based chiral stationary phase under polar ionic mode. The method was validated using a minimal salts medium inoculated with activated sludge as matrix. The method was selective and linear in the range of 10-800ng/ml, with a R(2)>0.99. The accuracy ranged from 85.0 percent to 103 percent, the recovery ranged from 79.9 percent to 103 percent, and the precision measured by the relative standard deviation (RSD) was <7.18 percent for intra-batch and <5.39 percent for inter-batch assays. The limits of quantification and detection for all enantiomers were 10ng/ml and 2.5ng/ml, respectively. The method was successfully applied to follow the biodegradation of the target pharmaceuticals using an activated sludge inoculum during a fifteen days assay. The results indicated slightly higher biodegradation rates for the S-enantiomeric forms of both beta-blockers. The presence of another carbon source maintained the enantioselective degradation pattern while enhancing biodegradation extent up to fourteen percent.
    Ecotoxicology and Environmental Safety 11/2012; 87. DOI:10.1016/j.ecoenv.2012.10.009 · 2.76 Impact Factor
    • "The choice of the CSP is based on the experience and the available literature, being often empirical by trial and error evaluation. However, some authors start with polysaccharides or macrocyclic antibiotics because of their broad application and the possibility to operate in normal, reverse phase, polar organic mode and polar ionic mode (Perrin et al. 2002a, b; Andersson et al. 2003; Cass et al. 2003; Sousa et al. 2004; Ates et al. 2008; Pirzada et al. 2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Many pharmaceutical pollutants are chiral, existing in the environment as a single enantiomer or as mixtures of the two enantiomers. In spite of their similar physical and chemical properties, the different spatial configurations lead the enantiomers to have different interactions with enzymes, receptors or other chiral molecules, which can give diverse biological response. Consequently, biodegradation process and ecotoxicity tend to be enantioselective. Despite numerous ongoing research regarding analysis and monitorization of pharmaceutical ingredients in the environment, the fate and effects of single enantiomers of chiral pharmaceuticals (CP) in the environment are still largely unknown. There are only few chiral analytical methods to accurately measure the enantiomeric fraction (EF) in environmental matrices and during biodegradation processes. Furthermore, the ecotoxicity studies usually consider the enantiomeric pair as unique compound. We reviewed the current knowledge about CP in the environment, as well as the chiral analytical methods to determine the EF in environmental matrices. The degradation and removal processes of CP of important therapeutic classes, usually detected in the environment, and their toxicity to aquatic organisms were also reviewed. On the other hand, this review demonstrate that despite the great importance of the stereochemistry in pharmaceutical science, pharmacology and organic chemistry, this is normally neglected in environmental studies. Therefore, CP in the environment need much more attention from the scientific community, and more research within this subject is required.
    Environmental Chemistry Letters 09/2012; 10(3). DOI:10.1007/s10311-011-0352-0 · 2.57 Impact Factor
Show more