Chiral column chromatography

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Chiral column chromatography [1] [2] is a variant of column chromatography that is employed for the separation of chiral compounds, i.e. enantiomers, in mixtures such as racemates or related compounds. The chiral stationary phase (CSP) is made of a support, usually silica based, on which a chiral reagent or a macromolecule with numerous chiral centers is bonded or immobilized. [3]

Contents

The chiral stationary phase can be prepared by attaching a chiral compound to the surface of an achiral support such as silica gel. For example, one class of the most commonly used chiral stationary phases both in liquid chromatography and supercritical fluid chromatography is based on oligosaccharides [4] such as Amylose Cellulose or Cyclodextrin (in particular with β-cyclodextrin, a seven sugar ring molecule) immobilized on silica gel.

The principle can be also applied to the fabrication of Monolithic HPLC columns [5] or Gas Chromatography columns. [6] or Supercritical Fluid Chromatography columns. [7]

The

Principle of Chiral Column Chromatography

The chiral stationary phase, CSP, can interact differently with two enantiomers, by a process known as chiral recognition. Chiral recognition depends on various interactions such as hydrogen bonding, π-π interaction, dipole stacking, inclusion complexation, steric, hydrophobic and electrostatic interaction, charge-transfer interactions, ionic interactions etc, between the analyte and the CSP, to form in-situ transient-diastereomeric complexes.

Most of the types of stationary phases can be classified as Pirkle type (Brush type), [8] [9] Protein-based, [10] Cyclodextrins based, [11] Polymer-based carbohydrates (polysaccharide-based CSPs), [12] Macrocyclic antibiotic, [13] Chiral crown ethers, [14] imprinted polymers, [15] etc.

Brush type columns (Pirkle Type)

The brush type, or Pirkle type chiral stationary phases [16] [17] are also called π-π Donnor-Acceptor columns. According to some theoretical models separation on these CSPs is based on a three-point attachment between the solute and the bonded chiral ligand on the surface of the stationary phase. These interactions may be attractive or repulsive in nature, depending on the mutual properties. Pirkle columns discriminate enantiomers by binding of one enantiomer with the chiral stationary phase, thereby forming a diastereomeric complex through π-π bonding, hydrogen bonding, steric interactions, and/or dipole stacking. Pirkle CSP can be categorized into three classes: [18]

(i)                 π-electron acceptor

(ii)               π-electron donor

(iii)             π-electron donor-π-electron acceptor.

Protein-based chiral stationary phases

A protein-based chiral stationary phase is based on silica-gel, on which a protein is immobilized or bonded. [19] The protein is based on many chiral centers, therefore the mechanism of chiral interaction between the protein and the analytes involves many interactions, such as hydrophobic and electrostatic interactions, hydrogen bonding and charge-transfer interactions, which may contribute to chiral recognition. Hydrophobic interactions between the protein and the analyte are affected by percent organic in the mobile phase. As the organic content increases, retention on protein-based columns decreases.

Polysaccharide chiral stationary phases

The naturally occurring polysaccharide form the basis for an important group of columns designed for chiral separation. The main polysaccharides are cellulose, amylose, chitosan, dextran, xylan, curdlan, and inulin. [20] Polysaccharide-based stationary phase have a high loading capacity, many chiral centers and complicated stereochemistry, and can be used for the separation of a wide range of compounds.

Polysaccharide-based chiral stationary phases have a wide application due to their high separation efficiency, selectivity, sensitivity and reproducibility under normal and reversed-phase conditions, as well as their broad applicability for structurally diversified compounds. [21] The mechanism of chiral interaction on the polysaccharide-based chiral stationary phase has not yet been elucidated. However, the following interactions are believed to play a role in the retention: [22]

(i) Hydrogen bonding interactions of the polar chiral analyte with carbamate groups on the CSP;

(ii)  π-π interactions between phenyl groups on the CSP and aromatic groups of the solute;

(i) Dipole-dipole interactions

(ii) Steric interactions due to the helical structure of the CSP.

These effects on the retention process originate also from the functionality of the derivatives of the polysaccharide, its average molecular weight, and size distribution, the solvent used to immobilize it on the macroporous silica support, and the nature of the macroporous silica support itself.

Cyclodextrin (CD) chiral stationary phases

Cyclodextrin (CD) chiral stationary phase is produced by partial degradation of starch by the enzyme cyclodextrin glycosyltransferase, followed by enzymatic coupling of the glucose units, forming a toroidal structure. CDs are cyclic oligosaccharides consisting of six (α CDs), seven (β CDs) and eight (γ CDs) glucopyranose units. The chiral recognition mechanism is based on a sort of inclusion complexation. Complexation involves the interaction of the hydrophobic portion of an analyte enantiomer with the non-polar interior of the cavity, while the polar functional groups can form a hydrogen bond with the polar hydroxyl chiral cavity space. The most important factor that determines whether the analyte molecule will fit into the cyclodextrin cavity is its size. The α-CD consists of 30 stereo-selective centers, β-CD consists of 35 stereo-selective centers and γ-CD consists of 40 stereo-selective centers. When the hydrophobic portion of the analyte is larger or smaller than the toroid's cavity size, inclusion will not occur.

Macrocyclic chiral stationary phases

Macrocyclic chiral stationary phases consist of a silica support, on which macrocyclic antibiotic molecules are bonded. [13] The commonly used macrocyclic antibiotics include rifamycin, glycopeptides (for example, avoparcin, teicoplanin, ristocetin A, vancomycin, and their analogs), polypeptide antibiotic thiostrepton, and aminoglycosides (for example, fradiomycin, kanamycin, and streptomycin). The macrocyclic antibiotics interact with the analyte through hydrogen bonds, dipole-dipole interactions with the polar groups of the analyte, ionic interactions and π-π interactions.

Chiral crown ether

Chiral crown stationary phases consist Crown ethers, immobilized or bonded to the support particles, are polyethers with a macrocyclic structure that can create host-guest complexes with alkali, earth-alkali metal ions, and ammonium cations. The skeleton of the cyclic structure is composed of oxygen and methylene groups arranged alternately. The electron-donating ether oxygens are positioned within the inner wall of the crown cavity, and are encircled by methylene groups in a collar-like arrangement. The chiral recognition is based on two distinct diastereomeric inclusion complexes that can be generated. The primary interactions facilitating complexation involve hydrogen bonds, formed between the three amine hydrogens and the oxygens of the macrocyclic ether, arranged in a tripod configuration. Additionally, ionic interactions, dipole-dipole interactions, or hydrogen bonds can occur between the carbocyclic groups and polar groups of the analytes, providing further support for the complexes.

Method Development

Method development of chiral chromatography is still done by screening of columns from the various classes of chiral columns. [23] While chiral separation mechanisms are understandable in certain scenarios, and the retention characteristics of analytes within the chromatographic columns can occasionally be elucidated, the precise combination of chiral stationary phases (CSPs) and mobile-phase compositions that required to effectively resolve a specific enantiomeric pair often remains elusive.

The chemistry of CSP ligands significantly influences the creation of in-situ diastereomeric complexes upon the stationary phase surface. However, other method's conditions, such as mobile-phase solvents, their composition, mobile phase additives and column temperature can play equally critical roles. The final resolution of the enantiomers is the outcome of combination of intermolecular forces, and even a subtle change in them can determine the success or failure of separation. This complexity prevents from establishing routine method-development protocols that are universally applicable to a diverse range of enantiomers. In fact, sometimes the outcome of previous unsuccessful experiments do not provide any clue for the subsequent steps. Therefore, in practice, a chiral method development laboratory settings, acts like a high-throughput screening protocol, [24] of conducting a systematic screening of various CSP's by advanced column switching devices, trying automatically and systematically various mobile-phase combinations, effectively employing a trial-and-error strategy. [23]

Because of the highly complex retention mechanism of a chiral stationary-phase due to chiral recognition, [17] whose principles have not been deciphered, it is often difficult, if not impossible to predict in advance the steps that can be successfully applied to the enantiomers at hand as part of method development. That's why the standard approach in the method development is high throughput screening, to evaluate or examine a series of stationary phases, using various mobile-phase combinations, to increase the chance of finding a suitable separation condition. [23]

See also

Related Research Articles

In chemical analysis, chromatography is a laboratory technique for the separation of a mixture into its components. The mixture is dissolved in a fluid solvent called the mobile phase, which carries it through a system on which a material called the stationary phase is fixed. Because the different constituents of the mixture tend to have different affinities for the stationary phase and are retained for different lengths of time depending on their interactions with its surface sites, the constituents travel at different apparent velocities in the mobile fluid, causing them to separate. The separation is based on the differential partitioning between the mobile and the stationary phases. Subtle differences in a compound's partition coefficient result in differential retention on the stationary phase and thus affect the separation.

<span class="mw-page-title-main">High-performance liquid chromatography</span> Technique in analytical chemistry

High-performance liquid chromatography (HPLC), formerly referred to as high-pressure liquid chromatography, is a technique in analytical chemistry used to separate, identify, and quantify specific components in mixtures. The mixtures can originate from food, chemicals, pharmaceuticals, biological, environmental and agriculture, etc, which have been dissolved into liquid solutions.

<span class="mw-page-title-main">Column chromatography</span> Method to isolate a compound in a mixture

Column chromatography in chemistry is a chromatography method used to isolate a single chemical compound from a mixture. Chromatography is able to separate substances based on differential adsorption of compounds to the adsorbent; compounds move through the column at different rates, allowing them to be separated into fractions. The technique is widely applicable, as many different adsorbents can be used with a wide range of solvents. The technique can be used on scales from micrograms up to kilograms. The main advantage of column chromatography is the relatively low cost and disposability of the stationary phase used in the process. The latter prevents cross-contamination and stationary phase degradation due to recycling. Column chromatography can be done using gravity to move the solvent, or using compressed gas to push the solvent through the column.

<span class="mw-page-title-main">Ion chromatography</span> Separates ions and polar molecules

Ion chromatography is a form of chromatography that separates ions and ionizable polar molecules based on their affinity to the ion exchanger. It works on almost any kind of charged molecule—including small inorganic anions, large proteins, small nucleotides, and amino acids. However, ion chromatography must be done in conditions that are one pH unit away from the isoelectric point of a protein.

<span class="mw-page-title-main">Molecular imprinting</span> Technique in polymer chemistry

Molecular imprinting is a technique to create template-shaped cavities in polymer matrices with predetermined selectivity and high affinity. This technique is based on the system used by enzymes for substrate recognition, which is called the "lock and key" model. The active binding site of an enzyme has a shape specific to a substrate. Substrates with a complementary shape to the binding site selectively bind to the enzyme; alternative shapes that do not fit the binding site are not recognized.

<span class="mw-page-title-main">Thin-layer chromatography</span> Technique used to separate non-volatile mixtures

Thin-layer chromatography (TLC) is a chromatography technique that separates components in non-volatile mixtures.

<span class="mw-page-title-main">Solid-phase extraction</span> Process to separate compounds by properties

Solid-phase extraction (SPE) is a solid-liquid extractive technique, by which compounds that are dissolved or suspended in a liquid mixture are separated, isolated or purified, from other compounds in this mixture, according to their physical and chemical properties. Analytical laboratories use solid phase extraction to concentrate and purify samples for analysis. Solid phase extraction can be used to isolate analytes of interest from a wide variety of matrices, including urine, blood, water, beverages, soil, and animal tissue.

<span class="mw-page-title-main">Chiral derivatizing agent</span> Reagent for converting a chemical compound to a chiral derivative

In analytical chemistry, a chiral derivatizing agent (CDA), also known as a chiral resolving reagent, is a derivatization reagent that is a chiral auxiliary used to convert a mixture of enantiomers into diastereomers in order to analyze the quantities of each enantiomer present and determine the optical purity of a sample. Analysis can be conducted by spectroscopy or by chromatography. Some analytical techniques such as HPLC and NMR, in their most commons forms, cannot distinguish enantiomers within a sample, but can distinguish diastereomers. Therefore, converting a mixture of enantiomers to a corresponding mixture of diastereomers can allow analysis. The use of chiral derivatizing agents has declined with the popularization of chiral HPLC. Besides analysis, chiral derivatization is also used for chiral resolution, the actual physical separation of the enantiomers.

Reversed-phase liquid chromatography (RP-LC) is a mode of liquid chromatography in which non-polar stationary phase and polar mobile phases are used for the separation of organic compounds. The vast majority of separations and analyses using high-performance liquid chromatography (HPLC) in recent years are done using the reversed phase mode. In the reversed phase mode, the sample components are retained in the system the more hydrophobic they are.

Mixed-mode chromatography (MMC), or multimodal chromatography, refers to chromatographic methods that utilize more than one form of interaction between the stationary phase and analytes in order to achieve their separation. What is distinct from conventional single-mode chromatography is that the secondary interactions in MMC cannot be too weak, and thus they also contribute to the retention of the solutes.

<span class="mw-page-title-main">Hydrophilic interaction chromatography</span> Type of chromatography

Hydrophilic interaction chromatography is a variant of normal phase liquid chromatography that partly overlaps with other chromatographic applications such as ion chromatography and reversed phase liquid chromatography. HILIC uses hydrophilic stationary phases with reversed-phase type eluents. The name was suggested by Andrew Alpert in his 1990 paper on the subject. He described the chromatographic mechanism for it as liquid-liquid partition chromatography where analytes elute in order of increasing polarity, a conclusion supported by a review and re-evaluation of published data.

Supercritical fluid chromatography (SFC) is a form of normal phase chromatography that uses a supercritical fluid such as carbon dioxide as the mobile phase. It is used for the analysis and purification of low to moderate molecular weight, thermally labile molecules and can also be used for the separation of chiral compounds. Principles are similar to those of high performance liquid chromatography (HPLC); however, SFC typically utilizes carbon dioxide as the mobile phase. Therefore, the entire chromatographic flow path must be pressurized. Because the supercritical phase represents a state whereby bulk liquid and gas properties converge, supercritical fluid chromatography is sometimes called convergence chromatography. The idea of liquid and gas properties convergence was first envisioned by Giddings.

Aqueous normal-phase chromatography (ANP) is a chromatographic technique that involves the mobile phase compositions and polarities between reversed-phase chromatography (RP) and normal-phase chromatography (NP), while the stationary phases are polar.

Electrochromatography is a chemical separation technique in analytical chemistry, biochemistry and molecular biology used to resolve and separate mostly large biomolecules such as proteins. It is a combination of size exclusion chromatography and gel electrophoresis. These separation mechanisms operate essentially in superposition along the length of a gel filtration column to which an axial electric field gradient has been added. The molecules are separated by size due to the gel filtration mechanism and by electrophoretic mobility due to the gel electrophoresis mechanism. Additionally there are secondary chromatographic solute retention mechanisms.

An enantiopure drug is a pharmaceutical that is available in one specific enantiomeric form. Most biological molecules are present in only one of many chiral forms, so different enantiomers of a chiral drug molecule bind differently to target receptors. Chirality can be observed when the geometric properties of an object is not superimposable with its mirror image. Two forms of a molecule are formed from a chiral carbon, these two forms are called enantiomers. One enantiomer of a drug may have a desired beneficial effect while the other may cause serious and undesired side effects, or sometimes even beneficial but entirely different effects. The desired enantiomer is known as an eutomer while the undesired enantiomer is known as the distomer. When equal amounts of both enantiomers are found in a mixture, the mixture is known as a racemic mixture. If a mixture for a drug does not have a 1:1 ratio of its enantiomers it is a candidate for an enantiopure drug. Advances in industrial chemical processes have made it economical for pharmaceutical manufacturers to take drugs that were originally marketed as a racemic mixture and market the individual enantiomers, either by specifically manufacturing the desired enantiomer or by resolving a racemic mixture. On a case-by-case basis, the U.S. Food and Drug Administration (FDA) has allowed single enantiomers of certain drugs to be marketed under a different name than the racemic mixture. Also case-by-case, the United States Patent Office has granted patents for single enantiomers of certain drugs. The regulatory review for marketing approval and for patenting is independent, and differs country by country.

<span class="mw-page-title-main">BIA Separations</span>

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<span class="mw-page-title-main">Capillary electrochromatography</span> Method of separating components of a mixture via electro-osmosis

In chemical analysis, capillary electrochromatography (CEC) is a chromatographic technique in which the mobile phase is driven through the chromatographic bed by electro-osmosis. Capillary electrochromatography is a combination of two analytical techniques, high-performance liquid chromatography and capillary electrophoresis. Capillary electrophoresis aims to separate analytes on the basis of their mass-to-charge ratio by passing a high voltage across ends of a capillary tube, which is filled with the analyte. High-performance liquid chromatography separates analytes by passing them, under high pressure, through a column filled with stationary phase. The interactions between the analytes and the stationary phase and mobile phase lead to the separation of the analytes. In capillary electrochromatography capillaries, packed with HPLC stationary phase, are subjected to a high voltage. Separation is achieved by electrophoretic migration of solutes and differential partitioning.

<span class="mw-page-title-main">Emanuel Gil-Av</span> Russian-Israeli chemist

Emanuel Gil-Av (Zimkin) was an Israeli chemist. The main emphasis of his work constituted chiral chromatography for the analytical separation of enantiomers.

Chiral analysis refers to the quantification of component enantiomers of racemic drug substances or pharmaceutical compounds. Other synonyms commonly used include enantiomer analysis, enantiomeric analysis, and enantioselective analysis. Chiral analysis includes all analytical procedures focused on the characterization of the properties of chiral drugs. Chiral analysis is usually performed with chiral separation methods where the enantiomers are separated on an analytical scale and simultaneously assayed for each enantiomer.

<span class="mw-page-title-main">Chiral thin-layer chromatography</span>

Chiral thin-layer chromatography is a variant of liquid chromatography that is employed for the separation of enantiomers. It is necessary to use either

References

Creative Commons by small.svg  This article incorporates text by Celina Nazareth and Sanelly Pereira available under the CC BY 4.0 license.

  1. ↑ Allenmark, Stig; Schurig, Volker (1997). "Chromatography on chiral stationary phases". Journal of Materials Chemistry. 7 (10): 1955–1963. doi:10.1039/A702403G. ISSN   1364-5501.
  2. ↑ Teixeira, Joana; Tiritan, Maria Elizabeth; Pinto, Madalena M. M.; Fernandes, Carla (2019). "Chiral Stationary Phases for Liquid Chromatography: Recent Developments". Molecules. 24 (5): 865. doi: 10.3390/molecules24050865 . ISSN   1420-3049. PMC   6429359 . PMID   30823495.
  3. ↑ Nazareth, Celina; Pereira, Sanelly (2020). "A Review on Chiral Stationary Phases for Separation of Chiral Drugs" (PDF). International Journal of Pharmaceutical and Phytopharmacological Research. 10 (3): 77–91.
  4. ↑ Yashima, Eiji (2001). "Polysaccharide-based chiral stationary phases for high-performance liquid chromatographic enantioseparation". Journal of Chromatography A. Chiral Separations. 906 (1): 105–125. doi:10.1016/S0021-9673(00)00501-X. ISSN   0021-9673. PMID   11215883.
  5. ↑ Yingjie Li; Chunhui Song; Lingyi Zhang; Weibing Zhang; Honggang Fu (January 2010). "Fabrication and evaluation of chiral monolithic column modified by β-cyclodextrin derivatives". Talanta . 80 (3): 1378–1384. doi:10.1016/j.talanta.2009.09.039. PMID   20006102.
  6. ↑ Yi-Ming Liu; Patricia Gordon; Shelby Green; Jonathan V. Sweedler (September 2000). "Determination of salsolinol enantiomers by gas chromatography-mass spectrometry with cyclodextrin chiral columns". Analytica Chimica Acta. 420 (1): 81–88. doi:10.1016/S0003-2670(00)00986-7.
  7. ↑ West, Caroline (2019). "Recent trends in chiral supercritical fluid chromatography". TrAC Trends in Analytical Chemistry. 120: 115648. doi: 10.1016/j.trac.2019.115648 . ISSN   0165-9936. S2CID   202884037.
  8. ↑ Fernandes, Carla; Tiritan, Maria Elizabeth; Pinto, Madalena (2013). "Small Molecules as Chromatographic Tools for HPLC Enantiomeric Resolution: Pirkle-Type Chiral Stationary Phases Evolution". Chromatographia. 76 (15): 871–897. doi:10.1007/s10337-013-2469-8. ISSN   1612-1112. S2CID   97668558.
  9. ↑ Tiritan, Maria Elizabeth; Pinto, Madalena; Fernandes, Carla (2023-04-12), Cass, Quezia Bezerra; Tiritan, Maria Elizabeth; Junior, João Marcos Batista; Barreiro, Juliana Cristina (eds.), "Pirkle Type", Chiral Separations and Stereochemical Elucidation (1 ed.), Wiley, pp. 325–362, doi:10.1002/9781119802280.ch9, ISBN   978-1-119-80225-9 , retrieved 2023-10-15
  10. ↑ Haginaka, Jun (2001). "Protein-based chiral stationary phases for high-performance liquid chromatography enantioseparations". Journal of Chromatography A. Chiral Separations. 906 (1): 253–273. doi:10.1016/S0021-9673(00)00504-5. ISSN   0021-9673. PMID   11215891.
  11. ↑ Xiao, Yin; Ng, Siu-Choon; Tan, Timothy Thatt Yang; Wang, Yong (2012). "Recent development of cyclodextrin chiral stationary phases and their applications in chromatography". Journal of Chromatography A. Chiral Separations and Enantioselectivity. 1269: 52–68. doi:10.1016/j.chroma.2012.08.049. ISSN   0021-9673. PMID   22959844.
  12. ↑ Geryk, Radim; Kalíková, Květa; Vozka, Jiří; Plecitá, Denisa; Schmid, Martin G.; Tesařová, Eva (2014-10-10). "Enantioselective potential of chiral stationary phases based on immobilized polysaccharides in reversed phase mode". Journal of Chromatography A. Enantioseparations - 2014. 1363: 155–161. doi:10.1016/j.chroma.2014.06.040. ISSN   0021-9673. PMID   24997511.
  13. 1 2 Armstrong, Daniel W.; Tang, Yubing.; Chen, Shushi.; Zhou, Yiwen.; Bagwill, Christina.; Chen, Jing-Ran. (1994). "Macrocyclic Antibiotics as a New Class of Chiral Selectors for Liquid Chromatography". Analytical Chemistry. 66 (9): 1473–1484. doi:10.1021/ac00081a019. ISSN   0003-2700.
  14. ↑ Li, Yanzhe; Sheng, Zhe; Zhu, Chuanlei; Yin, Wei; Chu, Changhu (2018). "Silica based click-dibenzo-18-crown-6-ether high performance liquid chromatography stationary phase and its application in separation of fullerenes". Talanta. 178: 195–201. doi: 10.1016/j.talanta.2017.07.037 . ISSN   0039-9140. PMID   29136812.
  15. ↑ Pu, Junli; Wang, Hongwei; Huang, Chao; Bo, Chunmiao; Gong, Bolin; Ou, Junjie (2022). "Progress of molecular imprinting technique for enantioseparation of chiral drugs in recent ten years". Journal of Chromatography A. 1668: 462914. doi:10.1016/j.chroma.2022.462914. ISSN   0021-9673. PMID   35220013. S2CID   246980680.
  16. ↑ Fernandes, Carla; Tiritan, Maria Elizabeth; Pinto, Madalena (2013-08-01). "Small Molecules as Chromatographic Tools for HPLC Enantiomeric Resolution: Pirkle-Type Chiral Stationary Phases Evolution". Chromatographia. 76 (15): 871–897. doi:10.1007/s10337-013-2469-8. ISSN   1612-1112. S2CID   97668558.
  17. 1 2 Magora, Amir; Abu-Lafi, Saleh; Levin, Shulamit (2000). "Comparison of the enantioseparation of racemic uridine analogs on Whelk-O 1 and ChiralPak-AD columns". Journal of Chromatography A. 866 (2): 183–194. doi:10.1016/S0021-9673(99)01108-5. ISSN   0021-9673. PMID   10670808.
  18. ↑ Fernandes, Carla; Phyo, Ye’ Zaw; Silva, Ana Sofia; Tiritan, Maria Elizabeth; Kijjoa, Anake; Pinto, Madalena M.M. (2018-04-03). "Chiral Stationary Phases Based on Small Molecules: An Update of the Last 17 Years". Separation & Purification Reviews. 47 (2): 89–123. doi:10.1080/15422119.2017.1326939. ISSN   1542-2119. S2CID   99405457.
  19. ↑ Zhu, Bolin; Xue, Mengyao; Liu, Beibei; Li, Qing; Guo, Xingjie (2019). "Enantioselective separation of eight antihistamines with α1-acid glycoprotein-based chiral stationary phase by HPLC: Development and validation for the enantiomeric quality control". Journal of Pharmaceutical and Biomedical Analysis. 176: 112803. doi:10.1016/j.jpba.2019.112803. ISSN   0731-7085. PMID   31442761. S2CID   201630751.
  20. ↑ Aboul-Enein, Hassan Y (2001). "High-performance liquid chromatographic enantioseparation of drugs containing multiple chiral centers on polysaccharide-type chiral stationary phases". Journal of Chromatography A. Chiral Separations. 906 (1): 185–193. doi:10.1016/S0021-9673(00)00950-X. ISSN   0021-9673. PMID   11215887.
  21. ↑ Nie, Y.; Liu, X.; Yang, X.; Zhao, Z. (2013). "Review: Recent Application of Chiral Liquid Chromatography-Tandem Mass Spectrometric Methods for Enantiomeric Pharmaceutical and Biomedical Determinations". Journal of Chromatographic Science. 51 (8): 753–763. doi: 10.1093/chromsci/bms209 . ISSN   0021-9665. PMID   23315149.
  22. ↑ Zhao, Binwu; Oroskar, Priyanka A.; Wang, Xiaoyu; House, David; Oroskar, Anil; Oroskar, Asha; Jameson, Cynthia; Murad, Sohail (2017). "The Composition of the Mobile Phase Affects the Dynamic Chiral Recognition of Drug Molecules by the Chiral Stationary Phase". Langmuir. 33 (42): 11246–11256. doi:10.1021/acs.langmuir.7b02337. ISSN   0743-7463. PMID   28826215.
  23. 1 2 3 Tarafder, Abhijit; Miller, Larry (2021). "Chiral chromatography method screening strategies: Past, present and future". Journal of Chromatography A. 1638: 461878. doi:10.1016/j.chroma.2021.461878. ISSN   0021-9673. PMID   33477025. S2CID   231677607.
  24. ↑ Lin, Jessica; Tsang, Charlotte; Lieu, Raymond; Zhang, Kelly (2020). "Method screening strategies of stereoisomers of compounds with multiple chiral centers and a single chiral center". Journal of Chromatography A. 1624: 461244. doi:10.1016/j.chroma.2020.461244. ISSN   0021-9673. PMID   32540081. S2CID   219700768.
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