Abstract: High-performance liquid chromatography (HPLC) is an ideal tool for enantiomeric separations of different drugs. In this study, the direct enantioseparation of bupropion, an atypical antidepressant structurally related to cathinone, was explored by using five chiral columns, including three based on derivatized cyclofructans, macrocyclic glycopeptide teicoplanin, and an immobilized amylose derivative under multimodal elution conditions. Baseline enantioseparation was obtained on the LarihcShell CF6-RN column, with derivatized cyclofructan 6, in the polar organic mode. The effects of the mobile-phase composition, type and content of major components, the nature and the amount of mobile-phase additives, and the column temperature on the retention, selectivity, and resolution were investigated to optimize enantioseparation. The calibration curve was linear in the range of 10-125 μg/ml for each enantiomer. The limits of detection and quantification were 0.1 and 0.3 μg/ml for both enantiomers of bupropion. The chiral recognition was controlled especially by H bonds, π-π, dipole-dipole interactions, and steric effects. Finally, the developed method was applied to the determination of bupropion in the commercially available drug.
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References: Costa R, Oliveira NG, Dinis-Oliveira RJ. Pharmacokinetic and pharmacodynamics of bupropion: integrative overview of relevant clinical and forensic aspects. Drug Metab Rev. 2019;51(3):293-313. doi:10.1080/03602532.2019.1620763.
Fang QK, Han Z, Grover P, Kessler D, Senanayake CH, Wald SA. Rapid access to enantiopure bupropion and its major metabolite by stereospecific nucleophilic substitution on an α-ketotriflate. Tetrahedron Asymmetry. 2000;11(18):3659-3663. doi:10.1016/S0957-4166(00)00349-9.
Reeves RR, Ladner ME. Additional evidence of the abuse potential of bupropion. J Clin Psychopharmacol. 2013;33(4):584-585. doi:10.1097/JCP.0b013e318295fe2f.
Castro-Puyana M, García MÁ, Marina ML. Enantiomeric separation of bupropion enantiomers by electrokinetic chromatography: quantitative analysis in pharmaceutical formulations. J Chromatogr B. 2008;875(1):260-265. doi:10.1016/j.jchromb.2008.09.008.
Pires BC, Coelho JF, Silva CF, et al. Enantioselective separation of bupropion and its major metabolite hydroxybupropion: an experimental and theoretical study. Chem Phys Lett. 2019;730:1-7. doi:10.1016/j.cplett.2019.05.035.
Lu Y, Wang H, Wang G, Wang Y, Gu X, Yan C. Preparation of 1 μm non-porous C18 silica gel stationary phase for chiral-pressurized capillary electrochromatography. Chin J Chromatogr. 2015;33(3):209-214. doi:10.3724/SP.J.1123.2014.11030.
Bhushan R, Batra S. Direct enantiomeric resolution of (±)-bupropion using chiral liquid chromatography. J Planar Chromatogr Modern TLC. 2013;26(6):491-495. doi:10.1556/JPC.26.2013.6.6.
Batra S, Bhushan R. Resolution of enantiomers of bupropion and its metabolites by liquid chromatography. Biomed Chromatogr. 2016;30(5):670-682. doi:10.1002/bmc.3572.
Munro JS, Walker TA. Bupropion hydrochloride: the development of a chiral separation using an ovomucoid column. J Chromatogr A. 2001;913(1-2):275-282. doi:10.1016/S0021-9673(01)00639-2.
Hermansson J, Grahn A. Optimization of the separation of enantiomers of basic drugs. Retention mechanisms and dynamic modification of the chiral bonding properties on an α1-acid glycoprotein column. J Chromatogr A. 1995;694(1):57-69. doi:10.1016/0021-9673(94)00936-4.
Munro JS, Gormley JP, Walker TA. Bupropion hydrochloride: the development of a chiral separation using a chiral AGP column. J Liq Chromatogr RT. 2001;24(3):327-339. doi:10.1081/JLC-100001337.
Coles R, Kharasch ED. Stereoselective analysis of bupropion and hydroxybupropion in human plasma and urine by LC/MS/MS. J Chromatogr B. 2007;857(1):67-75. doi:10.1016/j.jchromb.2007.07.007.
Teitelbaum AM, Flaker AM, Kharasch ED. Development and validation of a high- throughput stereoselective LC-MS/MS assay for bupropion, hydroxybupropion, erythrohydrobupropion and threohydrobupropion in human plasma. J Chromatogr B. 2016;1017-1018:101-113. doi:10.1016/j.jchromb.2016.02.032.
Zhu B, Li S, Zhou L, Li Q, Guo X. Simultaneous enantioselective determination of seven psychoactive drugs enantiomers in multi-specie animal tissues with chiral liquid chromatography coupled with tandem mass spectrometry. Food Chem. 2019;300:125241. doi:10.1016/j.foodchem.2019.125241.
Masters A, McCoy M, Jones DR, Desta Z. Stereoselective method to quantify bupropion and its three major metabolites, hydroxybupropion, erythro-dihydrobupropion, and threo-dihydrobupropion, using HPLC-MS/MS. J Chromatogr B. 2016;1015-1016:201-208. doi:10.1016/j.jchromb.2016.02.018.
Ali A, Suhail M, Alothman ZA, Alwarthan A. Chiral separation and modeling of baclofen, bupropion, and etodolac profens on amylose reversed phase chiral column. Chirality. 2017;29(7):386-397. doi:10.1002/chir.22717.
Armstrong DW, Tang Y, Chen S, Zhou Y, Bagwill C, Chen JR. Macrocyclic antibiotics as a new class of chiral selectors for liquid chromatography. Anal Chem. 1994;66(9):1473-1484. doi:10.1021/ac00081a019.
Ilisz I, Berkecz E, Péter A. Retention mechanism of HPLC enantioseparation on macrocyclic glycopeptide-based chiral stationary phases. J Chromatogr A. 2009;1216(10):1845-1860. doi:10.1016/j.chroma.2008.08.041.
Berkecz R, Tanács D, Péter A. Enantioselective liquid chromatographic separations using macrocyclic glycopeptide-based chiral selectors. Molecules. 2021;26(11):3380. doi:10.3390/molecules26113380.
Sun P, Wang C, Breitbach ZS, Zhang Y, Armstrong DW. Development of new HPLC chiral stationary phases based on native and derivatized cyclofructans. Anal Chem. 2009;81(24):10215-10226. doi:10.1021/ac902257a.
Sun P, Wang C, Padivitage NLT, et al. Evaluation of aromatic-derivatized cyclofructans 6 and 7 as HPLC chiral selectors. Analyst. 2011;136(4):787-800. doi:10.1039/C0AN00653J.
Gondová T, Petrovaj J, Kutschy P, Armstrong DW. Stereoselective separation of spiroindoline phytoalexins on R-naphthylethyl cyclofructan 6-based chiral stationary phase. J Chromatogr A. 2013;1272:100-105. doi:10.1016/j.chroma.2012.11.083.
Aboul-Enein HY, Kannappan V, Kanthiah S. Impact of cyclofructan derivatives as efficient chiral selector in chiral analysis: an overview. Chirality. 2022;34(2):364-373. doi:10.1002/chir.23396.
Berkecz R, Németi G, Péter A, Ilisz I. Liquid chromatographic enantioseparations utilizing chiral stationary phases based on crown ethers and cyclofructans. Molecules. 2021;26(15):4648. doi:10.3390/molecules26154648.
Xie SM, Yuan LM. Recent development trends for chiral stationary phase based on chitosan derivatives, cyclofructan derivatives and chiral porous materials in high performance liquid chromatography. J Sep Sci. 2019;42(1):6-20. doi:10.1002/jssc.201800656.
Shen J, Okamoto Y. Efficient separation of enantiomers using stereoregular chiral polymers. Chem Rev. 2016;116(3):1094-1138. doi:10.1021/acs.chemrev.5b00317.
Chankvetadze B. Recent trends in preparation, investigation and application of polysaccharide-based chiral stationary phases for separation of enantiomers in high-performance liquid chromatography. TrAC-Trends Anal Chem. 2020;122:115709. doi:10.1016/j.trac.2019.115709.
Scriba GKE. Chiral recognition in separation sciences. Part I: polysaccharide and cyclodextrin selectors. TrAC-Trends Anal Chem. 2019;120:115639. doi:10.1016/j.trac.2019.115639.
Food and Drug Administration. Q2(R1) Validation of analytical procedures: text and methodology guidance for industry. 2021.
Cheng L, Cai J, Fu Q, Ke Y. Efficient preparative separation of 6-(4-aminophenyl)-5-methyl-4,5-dihydro-3(2H)-pyridazinone enantiomers on polysaccharide-based stationary phases in polar organic solvent chromatography and supercritical fluid chromatography. J Sep Sci. 2019;42(15):2482-2490. doi:10.1002/jssc.201900253.
Asnin LD, Stepanova MV. Van't Hoff analysis in chiral chromatography. J Sep Sci. 2018;41(6):1319-1337. doi:10.1002/jssc.201701264.
Gotmar G, Fornstedt T, Guiochon G. Apparent and true enantioselectivity in enantioseparations. Chirality. 2000;12(7):558-564. doi:10.1002/1520-636X(2000)12:7%3C558::AID-CHIR2%3E3.0.CO;2-2.
Sepsey A, Horváth É, Catani M, Felinger A. The correctness of van't Hoff plots in chiral and achiral chromatography. J Chromatogr A. 2020;1611:460594. doi:10.1016/j.chroma.2019.460594.
Lajkó G, Grecsó N, Megyesi R, et al. Enantioseparation of β-carboline derivatives on polysaccharide- and strong cation exchanger-based chiral stationary phases. A comparative study. J Chromatogr A. 2016;1467:188-198. doi:10.1016/j.chroma.2016.05.040.
Berthod A. Chiral recognition in separation methods. Mechanisms and applications. Springer-Verlag; 2010. doi:10.1007/978-3-642-12445-7.
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