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.
Effects of the ester moiety on stereoselective hydrolysis of several propranolol prodrugs in rat tissues
Takahashi,Tamagawa,Sakano,Katagi,Mizuno
, p. 1401 - 1404 (1995)
The stereochemical characteristics of the hydrolysis of several ester- type prodrugs of propranolol, O-acetyl, O-propionyl, O-butyryl, O-pivaloyl and succinyl esters, were studied in phosphate buffer (pH 7.4), rat plasma and rat tissue homogenates. In phosphate buffer, no differences were observed in the hydrolysis rate between the esters of (R)- and (S)-propranolol. The effects of the ester moieties on the hydrolysis rate in phosphate buffer were in the following order: acetate > propionate > butyrate > succinate > pivalate. In rat plasma and tissue homogenates, the hydrolysis of the esters was accelerated, and stereoselective hydrolysis was observed. In plasma, the hydrolysis of the (R)-isomer was faster than that of the (S)-isomer except for the succinate ester. On the other hand, in the liver and intestine homogenates, the (S)-isomer was hydrolyzed faster than the (R)-isomer except for the succinate and pivalate esters in the liver homogenate. Also, the ratio of the hydrolysis rates (S/R) changed with the type of prodrug. As the length of the alkyl chain of the ester increased, the S/R ratio approached unity in liver and intestine homogenates but stayed almost constant in plasma. For the pivalate ester, stereoselective hydrolysis was observed in plasma and intestine homogenate but not in liver homogenate. The stereoselective hydrolysis of the succinate ester was observed only in intestine homogenate, but the S/R ratio was almost 1 in plasma, liver and intestine homogenates. No interconversion between (R)- and (S)-isomer was observed during the hydrolysis of any of the ester prodrugs. These results indicate that hydrolysis of ester-type prodrugs of propranolol occurs stereoselectively in rat tissues, and that its selectivity is dependent on the kind of tissue and prodrug.
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 with cellulose Tris (3,5-DimethylPhenylcarbamate) chiral stationary phase: Influence of coating times and coating amount on chiral discrimination
Wei, Qiuhong,Su, Hongjiu,Gao, Diannan,Wang, Shudong
, p. 164 - 173 (2019)
Coating cellulose tris (3,5-dimethylphenylcarbamate) (CDMPC) on silica gels with large pores have been demonstrated as an efficient way for the preparation of chiral stationary phase (CSP) for high-performance liquid chromatography (HPLC). During the process, a number of parameters, including the type of coating solvent, amount of coating, and the method for subsequent solvent removing, have been proved to affect the performance of the resultant CSPs. Coating times and the concentration of coating solution, however, also makes a difference to CSPs' performance by changing the arrangement of cellulose derivatives while remaining the coating amount constant, have much less been studied before, and thereby, were systematically investigated in this work. Results showed that CSPs with more coating times exhibited higher chiral recognition and column efficiency, suggesting that resolution was determined by column efficiency herein. Afterwards, we also investigated the effect of coating amount on the performance of CSPs, and it was shown that the ability of enantio-recognition did not increase all the time as the coating amount; and four of seven racemates achieved best resolution when the coating amount reached to 18.37%. At the end, the reproducibility of CDMPC-coated CSPs were further confirmed by two methods, ie, reprepared the CSP-0.15-3 and reevaluated the effect of coating times.
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
Enantioseparation of mandelic acid on vancomycin column: Experimental and docking study
Shahnani, Mostafa,Sefidbakht, Yahya,Maghari, Shokoofeh,Mehdi, Ahmad,Rezadoost, Hassan,Ghassempour, Alireza
, p. 1289 - 1298 (2020)
So far, no detailed view has been expressed regarding the interactions between vancomycin and racemic compounds including mandelic acid. In the current study, a chiral stationary phase was prepared by using 3-aminopropyltriethoxysilane and succinic anhydride to graft carboxylated silica microspheres and subsequently by activating the carboxylic acid group for vancomycin immobilization. Characterization by elemental analysis, Fourier transform infrared spectroscopy, solid-state nuclear magnetic resonance, and thermogravimetric analysis demonstrated effective functionalization of the silica surface. R and S enantiomers of mandelic acid were separated by the synthetic vancomycin column. Finally, the interaction between vancomycin and R/S mandelic acid enantiomers was simulated by Auto-dock Vina. The binding energies of interactions between R and S enantiomers and vancomycin chiral stationary phase were different. In the most probable interaction, the difference in mandelic acid binding energy was approximately 0.2 kcal/mol. In addition, circular dichroism spectra of vancomycin interacting with R and S enantiomers showed different patterns. Therefore, R and S mandelic acid enantiomers may occupy various binding pockets and interact with different vancomycin functions. These observations emphasized the different retention of R and S mandelic acid enantiomers in vancomycin chiral column.
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 human serum
Takahashi,Haginaka,Tamagawa,Nishihata,Yasuda,Katagi
, p. 356 - 357 (1990)
A direct high-performance liquid chromatographic method was developed for the assays of the enantiomers of O-acetyl propranolol. Using this procedure, the stereochemical characteristics on hydrolysis of racemic O-acetyl propranolol as a prodrug have been studied in phosphate buffer (pH 7.4) and in 90% human serum. In the phosphate buffer, no difference in the hydrolysis rate between the esters of (R)- and (S)-propranolol was observed. In 90% human serum, the hydrolysis of the esters was accelerated, and the hydrolysis rate of the ester of (R)-isomer was about three times faster than that of the ester of (S)-isomer. The interconversion between (R)- and (S)-isomer was not observed during the hydrolysis of prodrug in buffer and in human serum. These results indicated that hydrolysis of O-acetyl propranolol occurs stereoselectively in human serum.
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.
Enantiomeric separation of β-blockers and tryptophan using heparin as stationary and pseudostationary phases in capillary electrophoresis
Liu, Yi,Sombra, Lorena L.,Stege, Patricia W.
, p. 988 - 995 (2018)
The separation methods of the enantiomers of two β-blockers and tryptophan were studied using capillary electrochromatography with heparin covalently as well as non-covalently, bonded onto the capillary inner wall as stationary phase and electrokinetic chromatography with heparin as pseudostationary phase. In the case of heparin, used as a stationary phase, the method was unable to resolve enantiomers in both cases β-blockers and tryptophan. On the other hand, when heparin was used as a pseudostationary phase, the resolution of the enantiomers was obtained only with 3-aminopropyltriethoxysilane which were immobilised onto the inner phase of the capillary. The results of this study let us infer that the electrostatic, hydrophobic, and steric interactions were involved in the separation mechanisms. The separation was achieved in less than 10?minutes under the optimized conditions: 30?mM phosphate buffer (pH?2.5) with the adding of 15?mg/mL of heparin at 15°C and 10?kV. The usefulness of heparin as a chiral selector both in electrokinetic chromatography using 3-aminopropyltriethoxysilane attached to the capillary was demonstrated for the first time. The developed method was powerful, sensitive, and fast, and it could be considered an important alternative to conventional methods used for chiral separation.
