scholarly journals Chromatographic and Computational Studies on the Chiral Recognition of Sulfated β-Cyclodextrin on Enantiomeric Separation of Milnacipran

2020 ◽  
Author(s):  
Pranav Pathak ◽  
Evans C. Coutinho ◽  
Krishnapriya Mohanraj ◽  
Elvis Martis ◽  
Vikalp Jain
Keyword(s):  
Molecular Docking ◽  
Mobile Phase ◽  
Chiral Recognition ◽  
Cost Effective ◽  
Enantiomeric Separation ◽  
Enantiomeric Resolution ◽  
Recognition Mechanism ◽  
Column Temperature ◽  
Successful Resolution ◽  
Experimental Findings

<p>A new, cost-effective and fast chromatographic method using sulfated β-cyclodextrin (SβCD) as a chiral mobile phase additive (CMPA) was developed and validated for the enantiomeric separation of milnacipran. Milnacipran is an anti-depressant drug. Levo-milnacipran is the active enantiomer with less adverse effects than dextro-milnacipran. Hence, it is imperative to separate the enantiomers of milnacipran. Various parameters affecting enantiomeric resolution, for instance, the effect of type and concentration of cyclodextrins, the effect of pH of the mobile phase, effect of type and concentration of the organic solvent in the mobile phase and effect of type of achiral column, were investigated. We demonstrated successful resolution of enantiomers of milnacipran on reverse-phase HPLC with Kinetex C8 column (150x4.6mm, 5µ), using a mobile phase consisting of 18:82 v/v acetonitrile: 10mM sodium dihydrogen orthophosphate dihydrate buffer pH 3.0 (adjusted with orthophosphoric acid) containing 10mM SβCD with a flow rate 1.0 ml/minute. The column temperature was ambient and UV detection was carried out at 227 nm with an injection volume of 20µl. This method for enantiomeric separation of milnacipran was validated in accordance with ICH guidelines and successfully applied to the marketed formulation of Levomilnacipran. Furthermore, molecular docking was used to identify the chiral recognition mechanism. The results of molecular docking corroborated with our experimental findings.</p><p>A new, cost-effective and fast chromatographic method using sulfated β-cyclodextrin (SβCD) as a chiral mobile phase additive (CMPA) was developed and validated for the enantiomeric separation of milnacipran. Milnacipran is an anti-depressant drug. Levo-milnacipran is the active enantiomer with less adverse effects than dextro-milnacipran. Hence, it is imperative to separate the enantiomers of milnacipran. Various parameters affecting enantiomeric resolution, for instance, the effect of type and concentration of cyclodextrins, the effect of pH of the mobile phase, effect of type and concentration of the organic solvent in the mobile phase and effect of type of achiral column, were investigated. We demonstrated successful resolution of enantiomers of milnacipran on reverse-phase HPLC with Kinetex C8 column (150x4.6mm, 5µ), using a mobile phase consisting of 18:82 v/v acetonitrile: 10mM sodium dihydrogen orthophosphate dihydrate buffer pH 3.0 (adjusted with orthophosphoric acid) containing 10mM SβCD with a flow rate 1.0 ml/minute. The column temperature was ambient and UV detection was carried out at 227 nm with an injection volume of 20µl. This method for enantiomeric separation of milnacipran was validated in accordance with ICH guidelines and successfully applied to the marketed formulation of Levomilnacipran. Furthermore, molecular docking was used to identify the chiral recognition mechanism. The results of molecular docking corroborated with our experimental findings.</p><br>

scholarly journals Chromatographic and Computational Studies on the Chiral Recognition of Sulfated β-Cyclodextrin on Enantiomeric Separation of Milnacipran

2020 ◽  
Author(s):  
Pranav Pathak ◽  
Evans C. Coutinho ◽  
Krishnapriya Mohanraj ◽  
Elvis Martis ◽  
Vikalp Jain
Keyword(s):  
Molecular Docking ◽  
Mobile Phase ◽  
Chiral Recognition ◽  
Cost Effective ◽  
Enantiomeric Separation ◽  
Enantiomeric Resolution ◽  
Recognition Mechanism ◽  
Column Temperature ◽  
Successful Resolution ◽  
Experimental Findings

<p></p><p>A new, cost-effective and fast chromatographic method using sulfated β-cyclodextrin (SβCD) as a chiral mobile phase additive (CMPA) was developed and validated for the enantiomeric separation of milnacipran. Milnacipran is an anti-depressant drug. Levo-milnacipran is the active enantiomer with less adverse effects than dextro-milnacipran. Hence, it is imperative to separate the enantiomers of milnacipran. Various parameters affecting enantiomeric resolution, for instance, the effect of type and concentration of cyclodextrins, the effect of pH of the mobile phase, effect of type and concentration of the organic solvent in the mobile phase and effect of type of achiral column, were investigated. We demonstrated successful resolution of enantiomers of milnacipran on reverse-phase HPLC with Kinetex C8 column (150x4.6mm, 5µ), using a mobile phase consisting of 18:82 v/v acetonitrile: 10mM sodium dihydrogen orthophosphate dihydrate buffer pH 3.0 (adjusted with orthophosphoric acid) containing 10mM SβCD with a flow rate 1.0 ml/minute. The column temperature was ambient and UV detection was carried out at 227 nm with an injection volume of 20µl. This method for enantiomeric separation of milnacipran was validated in accordance with ICH guidelines and successfully applied to the marketed formulation of Levomilnacipran. Furthermore, molecular docking was used to identify the chiral recognition mechanism. The results of molecular docking corroborated with our experimental findings.</p><br><p></p>

scholarly journals Chromatographic and Computational Studies on the Chiral Recognition of Sulfated β-Cyclodextrin on Enantiomeric Separation of Milnacipran

2020 ◽  
Author(s):  
Pranav Pathak ◽  
Evans C. Coutinho ◽  
Krishnapriya Mohanraj ◽  
Elvis Martis ◽  
Vikalp Jain
Keyword(s):  
Molecular Docking ◽  
Mobile Phase ◽  
Chiral Recognition ◽  
Cost Effective ◽  
Enantiomeric Separation ◽  
Enantiomeric Resolution ◽  
Recognition Mechanism ◽  
Column Temperature ◽  
Successful Resolution ◽  
Experimental Findings

<p></p><p>A new, cost-effective and fast chromatographic method using sulfated β-cyclodextrin (SβCD) as a chiral mobile phase additive (CMPA) was developed and validated for the enantiomeric separation of milnacipran. Milnacipran is an anti-depressant drug. Levo-milnacipran is the active enantiomer with less adverse effects than dextro-milnacipran. Hence, it is imperative to separate the enantiomers of milnacipran. Various parameters affecting enantiomeric resolution, for instance, the effect of type and concentration of cyclodextrins, the effect of pH of the mobile phase, effect of type and concentration of the organic solvent in the mobile phase and effect of type of achiral column, were investigated. We demonstrated successful resolution of enantiomers of milnacipran on reverse-phase HPLC with Kinetex C8 column (150x4.6mm, 5µ), using a mobile phase consisting of 18:82 v/v acetonitrile: 10mM sodium dihydrogen orthophosphate dihydrate buffer pH 3.0 (adjusted with orthophosphoric acid) containing 10mM SβCD with a flow rate 1.0 ml/minute. The column temperature was ambient and UV detection was carried out at 227 nm with an injection volume of 20µl. This method for enantiomeric separation of milnacipran was validated in accordance with ICH guidelines and successfully applied to the marketed formulation of Levomilnacipran. Furthermore, molecular docking was used to identify the chiral recognition mechanism. The results of molecular docking corroborated with our experimental findings.</p><br><p></p>

A Simple and Cost-Effective Synthesis of Sulfated β-Cyclodextrin and Its Application as Chiral Mobile Phase Additive in the Separation of Cloperastine Enantiomers

2020 ◽  
Author(s):  
Krishna Deshpande ◽  
Pranav Pathak ◽  
Vishvas Joshi ◽  
Stephen barton ◽  
Krishnapriya Mohanraj
Keyword(s):  
Mobile Phase ◽  
Sulfamic Acid ◽  
Cost Effective ◽  
Pharmaceutical Formulations ◽  
Enantiomeric Separation ◽  
Reversed Phase ◽  
Recognition Mechanism ◽  
Beta Cyclodextrin ◽  
Chiral Mobile Phase Additive ◽  
Mobile Phase Additive

A new, simple and cost-effective method for the synthesis of sulfated beta-cyclodextrin (S-β-CD), one of the most widely used chiral mobile phase additive, using sulfamic acid as sulfonating agent has been described. The method was optimized and the acquired product was characterized and compared with a marketed Sigma Aldrich sulfated beta-cyclodextrin (S-β-CD1). Beta cyclodextrin (β-CD), hydroxypropyl beta-cyclodextrin (HP-β-CD), S-β-CD1 and S-β-CD2 were evaluated as chiral mobile phase additives (CMPAs) for the enantiomeric separation of cloperastine, an antitussive agent, using reversed-phase HPLC. Under the optimized conditions, a resolution of 3.14 was achieved within 15 minutes on an achiral Kromasil C<sub>8</sub> (150 x 4.6 mm, 5 µ) column with a mobile phase of 5mM monopotassium phosphate containing 10mM S-β-CD3 pH 3 and 45% methanol with a run time of 15 min. The method utilizing S-β-CD3 as CMPA was validated as per ICH guidelines and applied for the quantitative determination of cloperastine enantiomers in active pharmaceutical ingredients and pharmaceutical formulations. The selectivity changes imparted by S-β-CD were proven to be beneficial for chiral separation. The chiral recognition mechanism and elution order of the reported enantiomers were determined by simulation studies. It was observed that inclusion complex formation and hydrogen bonding are the major forces for the chiral resolution.

A Simple and Cost-Effective Synthesis of Sulfated β-Cyclodextrin and Its Application as Chiral Mobile Phase Additive in the Separation of Cloperastine Enantiomers

2020 ◽  
Author(s):  
Krishna Deshpande ◽  
Pranav Pathak ◽  
Vishvas Joshi ◽  
Stephen barton ◽  
Krishnapriya Mohanraj
Keyword(s):  
Mobile Phase ◽  
Sulfamic Acid ◽  
Cost Effective ◽  
Pharmaceutical Formulations ◽  
Enantiomeric Separation ◽  
Reversed Phase ◽  
Recognition Mechanism ◽  
Beta Cyclodextrin ◽  
Chiral Mobile Phase Additive ◽  
Mobile Phase Additive

A new, simple and cost-effective method for the synthesis of sulfated beta-cyclodextrin (S-β-CD), one of the most widely used chiral mobile phase additive, using sulfamic acid as sulfonating agent has been described. The method was optimized and the acquired product was characterized and compared with a marketed Sigma Aldrich sulfated beta-cyclodextrin (S-β-CD1). Beta cyclodextrin (β-CD), hydroxypropyl beta-cyclodextrin (HP-β-CD), S-β-CD1 and S-β-CD2 were evaluated as chiral mobile phase additives (CMPAs) for the enantiomeric separation of cloperastine, an antitussive agent, using reversed-phase HPLC. Under the optimized conditions, a resolution of 3.14 was achieved within 15 minutes on an achiral Kromasil C<sub>8</sub> (150 x 4.6 mm, 5 µ) column with a mobile phase of 5mM monopotassium phosphate containing 10mM S-β-CD3 pH 3 and 45% methanol with a run time of 15 min. The method utilizing S-β-CD3 as CMPA was validated as per ICH guidelines and applied for the quantitative determination of cloperastine enantiomers in active pharmaceutical ingredients and pharmaceutical formulations. The selectivity changes imparted by S-β-CD were proven to be beneficial for chiral separation. The chiral recognition mechanism and elution order of the reported enantiomers were determined by simulation studies. It was observed that inclusion complex formation and hydrogen bonding are the major forces for the chiral resolution.

scholarly journals Cost Effective, Efficient and Stability indicating analytical method validation for Ranolazine related by Reverse Phase High Performance Liquid Chromatography in drug substances

2020 ◽  
Vol 10 (6-s) ◽  
pp. 45-54
Author(s):  
Pushpendra Sharma ◽  
KLV Satyanarayana ◽  
G. Sri Hari
Keyword(s):  
Method Validation ◽  
Mobile Phase ◽  
High Performance ◽  
Cost Effective ◽  
Hplc Method ◽  
Pharmaceutical Dosage Forms ◽  
Column Temperature ◽  
Analytical Method Validation ◽  
Drug Substances ◽  
Ich Guidelines

A simple, selective, linear, precise and accurate RP-HPLC method was developed and validated for rapid assay of Ranolazine in drug substances. Isocratic elution at a flow rate of 1.4ml/min was employed on Hypersil BDS C18, 150 x 4.6 mm, 5µm or Equivalent at 40°C column temperature. The mobile phase consisted of Mobile phase-A: Mobile phase-B (55:45) (Disodium hydrogen orthophosphate buffer with pH 7.0 and Acetonitrile). The UV detection wavelength was at 205 nm. Linearity was observed in concentration range of 0.07-0.82 ppm for ranolazine impurity-I and concentration range of 0.07-0.78 ppm for ranolazine impurity-II. The retention time for Ranolazine was 7.6 min. The method was validated for validation parameter like specificity, force degradation, linearity, accuracy, precision and robustness as per the ICH guidelines. The proposed method can be successfully applied for the estimation of Ranolazine in pharmaceutical dosage forms. Keywords: Ranolazine, Method Validation, Drug Substances, HPLC

scholarly journals Analytical Separation of Closantel Enantiomers by HPLC

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7288
Author(s):  
Basma Saleh ◽  
Tongyan Ding ◽  
Yuwei Wang ◽  
Xiantong Zheng ◽  
Rong Liu ◽  
...  
Keyword(s):  
Trifluoroacetic Acid ◽  
Mobile Phase ◽  
High Performance ◽  
Enantiomeric Separation ◽  
Biological Research ◽  
The Novel ◽  
Column Temperature ◽  
Racemic Form ◽  
Mobile Phase Modifiers ◽  
Antiparasitic Drug

Closantel is an antiparasitic drug marketed in a racemic form with one chiral center. It is meaningful to develop a method for separating and analyzing the closantel enantiomers. In this work, two enantiomeric separation methods of closantel were explored by normal-phase high-performance liquid chromatography. The influences of the chiral stationary phase (CSP) structure, the mobile phase composition, the nature and proportion of different mobile phase modifiers (alcohols and acids), and the column temperature on the enantiomeric separation of closantel were investigated in detail. The two enantiomers were successfully separated on the novel CSP of isopropyl derivatives of cyclofructan 6 and n-hexane-isopropanol-trifluoroacetic acid (97:3:0.1, v/v/v) as a mobile phase with a resolution (Rs) of about 2.48. The enantiomers were also well separated on the CSP of tris-carbamates of amylose with a higher Rs (about 3.79) when a mixture of n-hexane-isopropanol-trifluoroacetic acid (55:45:0.1, v/v/v) was used as mobile phase. Thus, the proposed separation methods can facilitate molecular pharmacological and biological research on closantel and its enantiomers.

scholarly journals HPLC method validation for quantification of tetrahydrocurcumin in bulk drug and formulation

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Roopam Raut ◽  
Jessy Shaji
Keyword(s):  
Flow Rate ◽  
Mobile Phase ◽  
Wide Spectrum ◽  
Cost Effective ◽  
Hplc Method ◽  
Uv Detector ◽  
Column Temperature ◽  
Ich Guidelines ◽  
Recovery Study ◽  
Bulk Drug

Abstract Background Tetrahydrocurcumin (THC), the active metabolite of curcumin, is gaining popularity amongst scientist due to its wide spectrum of pharmacological activities, better stability and colourless nature. The objective of this study was to develop a sensitive, cost-effective RP-HPLC method for the estimation of THC in bulk drug substance and formulation. Results Efficient chromatographic separation was achieved on Hypersil BDS, C18 column, 250 mm × 4.6 mm, 5 μm column by isocratic elution with mobile phase comprising of acetonitrile: methanol: water (40:23:37% V/V); adjusted to a pH of 3.0 ± 0.05. The flow rate of the mobile phase was 1.0 ml/min with a column temperature of 25 °C. UV detector was used for the analysis and detection was carried out at 280 nm. The developed method was validated according to ICH guidelines with respect to system suitability, linearity, accuracy, precision and robustness. The theoretical plates were found to be more than 5800. The method showed linearity over the range of 4 to 60 μg/ml with R2 = 0.9998. The accuracy of the method in terms of recovery study was 98.23-99.99%. The %RSD for intra-day and inter-day precision were 0.272 and 0.275, respectively. The method was found to be robust with respect to change in wavelength, flow rate and column temperature. Conclusion The analytical method was found satisfactory on validation as per ICH guidelines. Hence, it can be routinely used for quantification of THC in bulk drug and formulation.

scholarly journals Direct Enantiomeric Separation and Determination of Hexythiazox Enantiomers in Environment and Vegetable by Reverse-Phase High-Performance Liquid Chromatography

2020 ◽  
Vol 17 (10) ◽  
pp. 3453
Author(s):  
Ping Zhang ◽  
Sheng Wang ◽  
Dongmei Shi ◽  
Yangyang Xu ◽  
Furong Yang ◽  
...  
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Mobile Phase ◽  
High Performance ◽  
Enantiomeric Separation ◽  
Reverse Phase ◽  
Column Temperature ◽  
Resolution Factor ◽  
Phase Temperature ◽  
Lower Temperature

In the present study, the direct enantiomeric separation of hexythiazox enantiomers on Lux cellulose-1, Lux cellulose-2, Lux cellulose-3, Lux cellulose-4, Lux amylose-1 and Chirapak IC chiral columns were carefully investigated by reverse-phase high-performance liquid chromatography (RP-HPLC). Acetonitrile/water and methanol/water were used as mobile phase at a flow rate of 0.8 mL·min−1. The effects of chiral stationary phase, temperature, thermodynamic parameters, mobile phase component and mobile phase ratio on hexythiazox enantiomers separation were fully evaluated. Hexythiazox enantiomers received a baseline separation on the Lux cellulose-3 column with a maximum resolution of Rs = 2.09 (methanol/water) and Rs = 2.74 (acetonitrile/water), respectively. Partial separations were achieved on other five chiral columns. Furthermore, Lux amylose-1 and Chirapak IC had no separation ability for hexythiazox enantiomers when methanol/water was used as mobile phase. Temperature study indicated that the capacity factor (k) and resolution factor (Rs) decreased with column temperature increasing from 10 °C to 40 °C. The enthalpy (ΔH) and entropy (ΔS) involved in hexythiazox separation were also calculated and demonstrated the lower temperature contributed to better separation resolution. Moreover, the residue analytical method for hexythiazox enantiomers in the environment (soil and water) and vegetable (cucumber, cabbage and tomato) were also established with reliable accuracy and precision under reverse-phase HPLC condition. Such results provided a baseline separation method for hexythiazox enantiomers under reverse-phase conditions and contributed to an environmental and health risk assessment of hexythiazox at enantiomer level.

scholarly journals Enantioselective Chromatographic Analysis of Formoterol Fumarate using Chiral Mobile Phase Additives and Achiral Core-Shell Column

2020 ◽  
Author(s):  
Pranav Pathak ◽  
Krishnapriya Mohanraj
Keyword(s):  
Mobile Phase ◽  
Cost Effective ◽  
Hplc Method ◽  
Enantiomeric Resolution ◽  
Factors Affecting ◽  
Mobile Phase Additives ◽  
Ich Guidelines ◽  
Chiral Mobile Phase Additive ◽  
Mobile Phase Additive ◽  
Chiral Mobile Phase Additives

<p>A simple, robust, cost-effective, and rapid RP-HPLC method was developed for the separation of enantiomers of formoterol. The separation was achieved by the chiral mobile phase additive technique on an achiral column. Formoterol is a bronchodilator that consists of 50:50 S, S-formoterol and R, R-formoterol. The bronchodilator activity is attributed to R, R-formoterol. Hence, it is important to develop a method to separate the enantiomers of formoterol. Various factors affecting enantiomeric resolution were investigated and optimized. The enantiomers of formoterol were successfully separated with a resolution of 2.57 with a run-time of 9 minutes. The method was validated in accordance with ICH guidelines. The validated method was successfully applied to the marketed formulation of arformoterol. </p>

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