13013-17-7Relevant articles and documents
Predictability of enantiomeric chromatographic behavior on various chiral stationary phases using typical reversed phase modeling software
Wagdy, Hebatallah A.,Hanafi, Rasha S.,El-Nashar, Rasha M.,Aboul-Enein, Hassan Y.
, p. 506 - 513 (2013)
Pharmaceutical companies worldwide tend to apply chiral chromatographic separation techniques in their mass production strategy rather than asymmetric synthesis. The present work aims to investigate the predictability of chromatographic behavior of enantiomers using DryLab HPLC method development software, which is typically used to predict the effect of changing various chromatographic parameters on resolution in the reversed phase mode. Three different types of chiral stationary phases were tested for predictability: macrocyclic antibiotics-based columns (Chirobiotic V and T), polysaccharide-based chiral column (Chiralpak AD-RH), and protein-based chiral column (Ultron ES-OVM). Preliminary basic runs were implemented, then exported to DryLab after peak tracking was accomplished. Prediction of the effect of % organic mobile phase on separation was possible for separations on Chirobiotic V for several probes: racemic propranolol with 97.80% accuracy; mixture of racemates of propranolol and terbutaline sulphate, as well as, racemates of propranolol and salbutamol sulphate with average 90.46% accuracy for the effect of percent organic mobile phase and average 98.39% for the effect of pH; and racemic warfarin with 93.45% accuracy for the effect of percent organic mobile phase and average 99.64% for the effect of pH. It can be concluded that Chirobiotic V reversed phase retention mechanism follows the solvophobic theory. 2013 Wiley Periodicals, Inc.
Enantioseparation by dual-flow countercurrent extraction: Its application to the enantioseparation of (±)-propranolol
Abe, Yoshihiro,Shoji, Tomoko,Fukui, Shikie,Sasamoto, Maki,Nishizawa, Hideyuki
, p. 1521 - 1524 (1996)
Enantioseparation of (±)-propranolol has been demonstrated by countercurrent extraction with a two-phase system composed of a chloroform solution of didodecyl L-tartrate (100 mM) and an acetate buffer (50 mM, pH 4.4) containing boric acid (100 mM). The free base of (±)-propranolol (1.6 g) was dissolved in the aqueous phase and extracted five times by means of dual-flow countercurrent extraction. After an additional five extractions for recovery, the crude R-(+)- or S-(-)-form was obtained from the aqueous extracts or organic extracts, respectively. They were isolated as their hydrochloride salts with a purity of 89.8% ee (R-form, 385.7 mg) and 88.3% ee (S-form, 429.5 mg), respectively. They were purified to over 99% ee by recrystallizing twice from 1-propanol.
HPLC-fluorescence method for the enantioselective analysis of propranolol in rat serum using immobilized polysaccharide-based chiral stationary phase
Alanazi, Amer M.,Hefnawy, Mohamed M.,Al-Majed, Abdulrahman A.,Al- Suwailem, Aymen K.,Kassem, Mohamed G.,Mostafa, Gamal A.,Attia, Sabry M.,Khedr, Mohammed M.
, p. 194 - 199 (2014)
A stereoselective high-performance liquid chromatographic (HPLC) method was developed and validated to determine S-(-)- and R-(+)-propranolol in rat serum. Enantiomeric resolution was achieved on cellulose tris(3,5- dimethylphenylcarbamate) immobilized onto spherical porous silica chiral stationary phase (CSP) known as Chiralpak IB. A simple analytical method was validated using a mobile phase consisted of n-hexane-ethanol-triethylamine (95:5:0.4%, v/v/v) at a flow rate of 0.6 mL min-1 and fluorescence detection set at excitation/emission wavelengths 290/375 nm. The calibration curves were linear over the range of 10-400 ng mL-1 (R = 0.999) for each enantiomer with a detection limit of 3 ng mL-1. The proposed method was validated in compliance with ICH guidelines in terms of linearity, accuracy, precision, limits of detection and quantitation, and other aspects of analytical validation. Actual quantification could be made for propranolol isomers in serum obtained from rats that had been intraperitoneally (i.p.) administered a single dose of the drug. The proposed method established in this study is simple and sensitive enough to be adopted in the fields of clinical and forensic toxicology. Molecular modeling studies including energy minimization and docking studies were first performed to illustrate the mechanism by which the active enantiomer binds to the β-adrenergic receptor and second to find a suitable interpretation of how both enantiomers are interacting with cellulose tris(3,5-dimethylphenylcarbamate) CSP during the process of resolution. The latter interaction was demonstrated by calculating the binding affinities and interaction distances between propranolol enantiomers and chiral selector. Chirality 26:194-199, 2014. 2014 Wiley Periodicals, Inc. Copyright
Simultaneous determination of propranolol enantiomers in plasma by high-performance liquid chromatography with fluorescence detection
Prakash,Koshakji,Wood,Blair
, p. 771 - 775 (1989)
A simple, rapid, and sensitive assay for the simultaneous quantification of the (-)- and (+)-propranolol in human and dog plasma is described using a reversed-phase high-performance liquid chromatography (HPLC) system with fluorescence detection. The method involves extraction of propranolol enantiomers from plasma into 1% 1-butanol in n-hexane at basic pH, followed by evaporation of the organic phase and the formation of diastereomeric derivatives with the chiral reagent (-)-menthyl chloroformate. (+)-Flecainide is used as the internal standard. The limiting concentration of each enantiomer that can be detected is 1 ng/mL plasma. In six normal human volunteers, who received a single oral dose of 80 mg of racemic propranolol, the plasma levels of the (-)-enantiomer were always higher than those of the (+)-enantiomer with a mean (-):(+) ratio of 1.38. The half-lives of both the enantiomers were similar (3.5 ± 0.3 h). In six normal male mongrel dogs given a single intraportal dose of 40 mg of racemic propranolol, the plasma levels of the (-)-enantiomer were always lower than those of the (+)-enantiomer with a mean (-):(+) ratio of 0.48. The half-life of the (-)-enantiomer (73.3 ± 16.2 min) was shorter than that of the (+)-enantiomer (87.1 ± 18.1 min).
Stereoselective hydrolysis of O-acetyl propranolol as prodrug in rat tissue homogenates
Takahashi,Tamagawa,Haginaka,Yasuda,Katagi,Mizuno
, p. 226 - 227 (1992)
The stereochemical characteristics of the hydrolysis of O-acetyl propranolol were studied using phosphate buffer (pH 7.4), rat plasma, and rat tissue homogenates. In the phosphate buffer, no difference was observed in the hydrolysis rate between the esters of (R)- and (S)-propranolol. In rat plasma and tissue homogenates, hydrolysis of the ester was both accelerated and stereoselective. Hydrolysis of O-acetyl (R)-propranolol was five times faster than that of the (S)-isomer in rat plasma. However, in the liver and intestine homogenates, the (S)-isomer was hydrolyzed faster than the (R)- isomer. Interconversion between the (R)- and (S)-isomers was not observed under the experimental conditions. The same stereoselective hydrolysis was also observed with racemic O-acetyl propranolol. However, observed rate constants for the hydrolysis were lower than those for the pure isomers. These results indicate that enzymatic hydrolysis of O-acetyl propranolol occurred stereoselectively and the selectivity of the plasma enzyme was different from those of liver and intestine enzymes.
Practical chemoenzymatic synthesis of both enantiomers of propranolol
Bevinakatti,Banerji
, p. 5372 - 5375 (1991)
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Application of cyclam-capped β-cyclodextrin-bonded silica particles as a chiral stationary phase in capillary electrochromatography for enantiomeric separations
Gong, Yinhan,Lee, Hian Kee
, p. 1348 - 1354 (2003)
Two novel types of substituted cyclam-capped β-cyclodextrin (β-CD)-bonded silica particles have been prepared and used as chiral stationary phases in capillary electrochromatography (CEC). The two stationary phases have a chiral selector with three recognition sites: β-CD, cyclam, and the latter's sidearm. They exhibit excellent enantioselectivities in CEC for a wide range of compounds as a result of the cooperative functioning of the anchored β-CD and cyclam. After inclusion of the metal ion (Ni2+) from the running buffer into the substituted cyclams and their sidearm ligands, the bonded stationary phases become positively charged and can provide extra electrostatic interactions with ionizable solutes and enhance the dipolar interactions with some polar neutral solutes. This enhances the host-guest interaction with some solutes and improves chiral recognition and enantioselectivity. These new types of stationary phases exhibit great potential for fast chiral separations in CEC.
Chemoenzymatic synthesis of (R)- and (S)-atenolol and propranolol employing lipase catalyzed enantioselective esterification and hydrolysis
Damle, Subhash V.,Patil, Prashant N.,Salunkhe, Manikrao M.
, p. 3855 - 3862 (1999)
Chemoenzymatic synthesis of (R) - and (S) - atenolol and propranolol employing lipase catalyzed enantioselective esterification and hydrolysis is described.
Chemoenzymatic synthesis of (R)- and (S)-propranolol using an engineered epoxide hydrolase with a high turnover number
Kong, Xu-Dong,Yu, Hui-Lei,Yang, Sheng,Zhou, Jiahai,Zeng, Bu-Bing,Xu, Jian-He
, p. 275 - 281 (2015)
Simultaneous synthesis of the R- and S-enantiomers of biologically active propranolol, a typical β-blocker, was achieved in high optical purity via an epoxide hydrolase-catalyzed resolution of racemic α-naphthyl glycidyl ether (rac-1). A preparative resolution of 100 g/L rac-1 was accomplished with high enantioselectivity (E = 92) using a variant of Bacillus megaterium epoxide hydrolase (BmEHF128T). A biphasic system (isopropyl ether/isooctane/aqueous) was used, in which the product 3-(1′-naphthyloxy)-propane-1,2-diol (2) precipitated instantly, facilitating its separation and increasing the enantiopurity of (R)-2 (>99.5% ee). This enzymatic resolution had a total turnover number of 70,000, affording enantiopure epoxide (S)-1 (>99% ee) and 1,2-diol (R)-2 (>99% ee) in 45.3% and 42.4% yields, respectively. (R)-2 and (S)-1 were subsequently converted to (R)- and (S)-propranolol (3) (>99% ee) in overall yields of 31.4% and 44.8%. To the best of our knowledge, this is the best case for enzymatic resolution of rac-1 using an epoxide hydrolase, giving high space-time yields [136 g L-1 days-1 for (S)-1 and 139 g L-1 days-1 for (R)-2] under mild reaction conditions. It provides a new and eco-friendly route that complements other methods using organometallic catalysts.
Electrically assisted liquid-phase microextraction combined with capillary electrophoresis for quantification of propranolol enantiomers in human body fluids
Tabani, Hadi,Fakhari, Ali Reza,Shahsavani, Abolfath,Gharari Alibabaou, Hossein
, p. 260 - 267 (2014)
In this study, electromembrane extraction (EME) combined with cyclodextrin (CD)-modified capillary electrophoresis (CE) was applied for the extraction, separation, and quantification of propranolol (PRO) enantiomers from biological samples. The PRO enantiomers were extracted from aqueous donor solutions, through a supported liquid membrane (SLM) consisting of 2-nitrophenyl octyl ether (NPOE) impregnated on the wall of the hollow fiber, and into a 20-μL acidic aqueous acceptor solution into the lumen of hollow fiber. Important parameters affecting EME efficiency such as extraction voltage, extraction time, pH of the donor and acceptor solutions were optimized using a Box-Behnken design (BBD). Then, under these optimized conditions, the acceptor solution was analyzed using an optimized CD-modified CE. Several types of CD were evaluated and best results were obtained using a fused-silica capillary with ammonium acetate (80 mM, pH 2.5) containing 8 mM hydroxypropyl-β-CD as a chiral selector, applied voltage of 18 kV, and temperature of 20C. The relative recoveries were obtained in the range of 78-95%. Finally, the performance of the present method was evaluated for the extraction and determination of PRO enantiomers in real biological samples. Chirality 26:260-267, 2014. 2014 Wiley Periodicals, Inc.
Preparation of a novel hydroxypropyl-γ-cyclodextrin functionalized monolith for separation of chiral drugs in capillary electrochromatography
Deng, Miaoduo,Xue, Mengyao,Liu, Yanru,Zhao, Min
, p. 188 - 195 (2021)
In this study, a novel hydroxypropyl-γ-cyclodextrin (HP-γ-CD) functionalized monolithic capillary column was prepared by one-pot sequential strategy and used for chiral separation in capillary electrochromatography for the first time. In one pot, GMA-HP-γ-CD as functional monomer was allowed to be formed via the ring opening reaction between HP-γ-CD and glycidyl methacrylate (GMA) catalyzed by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and then copolymerized directly with ethylene dimethacrylate (EDMA) and 2-acrylamido-2-methyl propane sulfonic acid (AMPS) in the presence of porogenic solvents via thermally initiated free radical polymerization. The preparation conditions of monoliths were optimized. Enantiomer separations of six chiral drugs including pindolol, clorprenaline, tulobuterol, clenbuterol, propranolol, and tropicamide were achieved on the monolith. Among them, pindolol, clorprenaline, and tropicamide were baseline separated with resolution values of 1.62, 1.73, and 1.55, respectively. The mechanism of enantiomer separation was discussed by comparison of the HP-γ-CD and HP-β-CD functionalized monoliths.
Preparation of polar group derivative β-cyclodextrin bonded hydride silica chiral stationary phases and their chromatography separation performances
Zhao, Baojing,Li, Lan,Wang, Yuting,Zhou, Zhiming
, p. 643 - 649 (2018/11/27)
Three novel β-cyclodextrin compounds derived with piperidine which is flexible, L-proline containing a chiral center, ionic liquid with 3,5-diamino-1,2,4-triazole as the cation were designed and synthesized as chiral selectors for enantiomer separation, whose name were (mono-6-deoxy-6-(piperidine)-β-cyclodextrin, mono-6-deoxy-6-(L-proline)-β-cyclodextrin, mono-6-deoxy-6-(3,5-diamino-1,2,4-triazole)-β-cyclodextrin, multi-substituted 3,5-diamino-1,2,4- triazole-(p-toluenesulfonic)-β-cyclodextrin), respectively. In addition, to enhance the polarity of chiral stationary phases, hydrosilylation and silylation reactions were implemented to derive ordinary silica, the common used selector carrier, to hydride silica, whose surface is covered with proton. 31 pyrrolidine compounds and some chiral drugs were tested in both polar organic mobile phase mode and normal mobile phase mode. 6-Deoxy-6-L-proline-β-cyclodextrin-CSP showed satisfactory separations in polar organic mobile phase mode and exihibited a strong separation capability in different pH values; multi-substituted 3,5-diamino-1,2,4-triazole-(p-toluenesulfonic)-β-cyclodextrin-CSP can separate pyrrolidine compounds in both mobile phase modes with high resolutions and separation efficiency compared to commercially available CSPs, making it to be the most valuable object to study. The composition of mobile phase, type of stationary phase as well as the peak problem of chromatograms was discussed deeply.
