Separation Of Propranolol Enantiomers Research Articles

Synthesis of camphor sulfonic acid derivatives modified Mg/Al-LDH for efficient separation of propranolol enantiomers

Designing chiral adsorption separation material with high enantioselectivity and stability is a promising route to realize the enantioselective recognition and separation of racemic molecules. Here, for the first time, camphor sulfonic acid derivatives (CSA) were synthesized as a chiral resolving agent, and it was modified on Mg/Al layered double hydroxide (Mg/Al-LDH) through electrostatic self-assembly to construct functionalized chiral adsorption separation material (CSA@LDH), which could be served as an adsorbent for enantioselective recognition and separation of propranolol enantiomers (R,S-PRO). The CSA@LDH maintained the advantage of limited chiral space in layered structures to achieve the selective enrichment of R-PRO, and the e.e.% value of single separation could reach 19.5%. Meanwhile, density functional theory (DFT) calculations supported that chiral recognition and separation were ascribed to the discrepancy in affinities stemming from the difference of π-π interaction force and hydrogen bonding capacity of CSA with R,S-PRO. Hence, considering the superior ability of hydrogen bond coordination and stereocontrol of camphor sulfonic acid derivatives, it is expected to be more widely used as a chiral resolving agent for other enantiomeric recognition and separation.

Chiral Separation of Propranolol Enantiomers by Oxidized Multiwalled Carbon Nanotubes/β-cyclodextrin Impregnated Thin-layer Chromatography

Chiral Separation of Propranolol Enantiomers by Oxidized Multiwalled Carbon Nanotubes/β-cyclodextrin Impregnated Thin-layer Chromatography

Comparative NMR and MS studies on the mechanism of enantioseparation of propranolol with heptakis(2,3‐diacetyl‐6‐sulfo)‐β‐cyclodextrin in capillary electrophoresis with aqueous and non‐aqueous electrolytes

In our recent studies, the reversal of the enantiomer migration order (EMO) was observed with heptakis (2,3-dimethyl-6-sulfo)-β-CD (HDMS-β-CD) when aqueous electrolyte was changed with nonaqueous electrolyte in CE. One-dimensional rotating frame nuclear Overhauser effect spectroscopy experiments prevailed that an inclusion complex was formed between the analyte and the chiral selector in the aqueous buffer, whereas an external complex resulted when a methanolic electrolyte was employed. In the case of the similarly substituted heptakis (2,3-diacetyl-6-sulfo)-β-CD (HDAS-β-CD), the external complex was observed in the aqueous buffer but an inclusion complex was formed in methanolic electrolyte. In contrast to heptakis (2,3-dimethyl-6-sulfo)-β-CD, no reversal of the enantiomer migration order was observed with HDAS-β-CD. In the present study, further mechanisms of enantioselective recognition and separation of propranolol enantiomers with HDAS-β-CD were investigated by using different techniques of nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry. To the best of our knowledge, enantioselective nuclear Overhauser effect was observed for the first time in this study.

Enantiomeric separation of propranolol by normal phase chiral liquid chromatography coupled with tandem mass spectrometry

A rapid and sensitive method was developed and validated using a normal phase liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) for determination of propranolol enantiomers in pharmaceuticals. Sample preparation involved a single extraction step by the addition of methanol. Separation of propranolol enantiomers was achieved on a Chiralcel OD-H chiral column using a mobile phase consisting of n-hexane-ethanol-ammonia (70:30:0.4, v/v/v), and the flow rate was 0.40 mL/min for 20 min. The analyte was monitored by tandem mass spectrometry with electrospray positive ionization in multiple reaction monitoring (MRM) mode, using the transitions of m/z 260.2 --> 116.0. Propranolol enantiomers can be completely separated. The linear range was 2.5-1000 microg/L, and the limit of quantification (LOQ) was 2.5 microg/L. The values for within day and between day precisions and accuracies were well within the generally accepted criteria for analytical methods. The relative standard deviations (RSDs) were less than 2.64%, and the recoveries of the two enantiomers were 99.08%-102.58% and 100.21%-103.16%, respectively. The separation method is accurate, convenient, reliable, efficient, and can be subsequently used for quality control of propranolol enantiomers in pharmaceuticals.

Separation of propranolol enantiomers by CE using sulfated β‐CD derivatives in aqueous and non‐aqueous electrolytes: Comparative CE and NMR study

Separations using CE employing non-aqueous BGE are already as well established as separations in aqueous buffers. The separation mechanisms in achiral CE with non-aqueous BGEs are most likely similar to those in aqueous buffers. However, for the separation of enantiomers involving their interaction with chiral buffer additives, the interaction mechanisms might be very different in aqueous and non-aqueous BGEs. While the hypothesis regarding distinct mechanisms of enantiomer separations in aqueous and non-aqueous BGEs has been mentioned in several papers, no direct proof of this hypothesis has been reported to date. In the present study, the enantiomers of propranolol were resolved using CE in aqueous and non-aqueous methanolic BGEs with two single isomer sulfated derivatives of beta-CD, namely heptakis (2,3-diacetyl-6-sulfo)-beta-CD and heptakis (2,3-dimethyl-6-sulfo)-beta-CD. The enantiomer migration order of propranolol was inverted when an aqueous BGE was replaced with non-aqueous BGE in the case of heptakis (2,3-dimethyl-6-sulfo)-beta-CD but remained the same in the case of heptakis (2,3-diacetyl-6-sulfo)-beta-CD. The possible molecular mechanisms leading to this reversal of enantiomer migration order were studied by using nuclear overhauser effect spectroscopy in both aqueous and non-aqueous BGEs.

Separation of propranolol enantiomers through membranes based on chiral derivatized polysulfone

The characterization of new synthesized chiral polymeric membranes, based in polysulfone polymer is here reported. Polysulfone was derivatized to chiral polysulfone, by bonding covalently the chiral carrier, N-dodecyl-4( R)-hydroxy- l-proline, to the polymer matrix. Two different chiral polysulfones, referred to as CPS A and CPS B, have been synthesized and used in the preparation of chiral polymeric membranes. However, as a consequence of the limited CPS B solubility, only CPS A resulted adequate to obtain useful membranes. Therefore, various chiral polysulfone membranes containing different amounts of CPS A in unmodified polysulfone (PS) were prepared and properly characterized by scanning electron microscopy (SEM) and by enantioselective transport experiments of racemic propranolol. Dialysis transport experiments allowed us to determine the influence of the carrier content in the membrane on the transport rate and on enantiomer separation. Membranes containing a CPS A/PS ratio of 1:3 showed an alpha value of 1.1 at 96 h of performance. Modelling of the propranolol transport rate is also performed.

An evaluation of the structural requirements for the separation of propranolol enantiomers on Pirkle phases following achiral derivatisation

The chromatographic performance of a series of isocyanate and isothiocyanate derivatives of (±)-propranolol has been investigated on three Pirkle-type chiral stationary phases (CSP's), 3,5-dinitrobenzoylphenylglycine (PHE), 3,5-dinitrobenzoylleucine (LEU) and phenethylpropylurea (PEPU). The reaction yield is independent of the substituent group but is affected by choice of solvent. The urea or thiourea derivative group formed is responsible for any separation observed on the amino acid based phases, the retention being related to structure. The structure-retention relationship is not apparent for the π-basic PEPU phase, moreover resolution is not simply related to retention for all three phases. Inversion of elution order of the enantiomers is observed with certain derivatives on the LEU column. The naphthyl and nitrophenyl derivatives generally exhibit enhanced retention, with the naphthylurea derivative generally giving the best resolution on these phases.