Enantiomeric separation of optically active pyridazinone derivatives by chiral HPLC

AbstractStarting from methyl cycloheptatrienyl-1-carboxylate, 6-acylation was successfully achieved employing glutaryl chloride in the presence of AlCl3 under controlled reaction conditions to furnish keto carboxylic acid product. After protection of this keto carboxylic acid as tert-butyl ester, reagent-controlled enantioselective reductions delivered configuration-defined methyl-6-hydroxylalkyl cycloheptatriene-1-carboxylates with up to 80% ee. Whereas simple NaBH4 reduction of the keto carboxylic acid and subsequent lactonization afforded a methyl-6-tetrahydropyranonyl cycloheptatriene-1-carboxylate. Resolution using chiral HPLC delivered the product enantiomers with up to >99% ee Finally, ECD analyses enabled structure elucidation. The products are used as key intermediates in enantioselective 6,11-methylene-lipoxin B4 syntheses.

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Development and Validation of a Chiral HPLC Method for Quantitative Analysis of Enantiomeric Escitalopram

Dhaka University Journal of Pharmaceutical Sciences ◽

10.3329/dujps.v16i2.35253 ◽

2018 ◽

Vol 16 (2) ◽

pp. 165-172 ◽

Cited By ~ 1

Author(s):

Asma Rahman ◽

Mohammad Rashedul Haque ◽

M Muhibur Rahman ◽

Mohammad A Rashid

Keyword(s):

Pharmaceutical Preparations ◽

Enantiomeric Separation ◽

Hplc Method ◽

Enantiomeric Purity ◽

Chiral Hplc ◽

Average Percentage ◽

Quantitation Limit ◽

Relative Standard ◽

Development And Validation

In the present study a rapid, accurate and precise chiral HPLC method was developed and validated for enantiomeric separation of racemate citalopram and escitalopram according to the guidelines of United States of Pharmacopeia (USP) and International Conference on Harmonization (ICH). The chiral chromatographic separation was achieved with ammonium acetate/ ethanol/ 2-propanol/ methylene dichloride (100 : 150 : 70 : 30, v/v) at a flow rate of 0.5 ml/min using a chiral CD-PH column. The HPLC analyses were monitored at 254 nm. The method showed a good linearity with regression coefficient (r2) of 0.998 in the range of 20.0-70.0 μg/ml for escitalopram. The detection limit (LOD), quantitation limit (LOQ) and average percentage of recovery for escitalopram were found to be 2.54, 7.68 μg/ml and 100.28% to 102.86%, respectively. The percentage of relative standard deviation (%RSD) for intra- and inter- day precision were found as 0.16% and 0.09%, respectively. The established method proved as reproducible with a %RSD value of less than 2 and having the robustness within specified limit. The present study also showed the enantiomeric purity or excess (%ee) of seven pharmaceutical preparations of escitalopram. Thus the proposed chiral method can be applied for the enantiomeric purity determination of escitalopram formulations.Dhaka Univ. J. Pharm. Sci. 16(2): 165-172, 2017 (December)

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A validated chiral HPLC method for the enantiomeric separation of tolterodine tartarate

Journal of Pharmaceutical and Biomedical Analysis ◽

10.1016/j.jpba.2004.03.026 ◽

2004 ◽

Vol 35 (5) ◽

pp. 1279-1285 ◽

Cited By ~ 14

Author(s):

Y.Ravindra Kumar ◽

G. Ramulu ◽

V.V. Vevakanand ◽

Gopal Vaidyanathan ◽

Keesari srinivas ◽

...

Keyword(s):

Enantiomeric Separation ◽

Hplc Method ◽

Chiral Hplc

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Lipase-catalyzed enantiomeric separation of 1-aryloxy-3-thiocyanatopropan-2-ols: an attempt to prepare optically active thiiranes

Tetrahedron Asymmetry ◽

10.1016/j.tetasy.2005.05.007 ◽

2005 ◽

Vol 16 (12) ◽

pp. 2149-2156 ◽

Cited By ~ 8

Author(s):

Edyta Łukowska ◽

Jan Plenkiewicz

Keyword(s):

Enantiomeric Separation ◽

Optically Active

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Enantiomeric separation of tocainide and its analogues on an optically active crown ether-based stationary phase by liquid chromatography

Journal of Chromatography A ◽

10.1016/s0021-9673(03)00540-5 ◽

2003 ◽

Vol 996 (1-2) ◽

pp. 233-237 ◽

Cited By ~ 23

Author(s):

Myung Ho Hyun ◽

Hye Jung Min ◽

Yoon Jae Cho

Keyword(s):

Liquid Chromatography ◽

Crown Ether ◽

Stationary Phase ◽

Enantiomeric Separation ◽

Optically Active

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Development and Validation of a Chiral Liquid Chromatographic Assay for Enantiomeric Separation and Quantification of Verapamil in Rat Plasma: Stereoselective Pharmacokinetic Application

Molecules ◽

10.3390/molecules26072091 ◽

2021 ◽

Vol 26 (7) ◽

pp. 2091

Author(s):

Mostafa S. Mohammed ◽

Mohamed M. Hefnawy ◽

Abdulrhman A. Al-Majed ◽

Haitham K. Alrabiah ◽

Nasser A. Algrain ◽

...

Keyword(s):

Solid Phase Extraction ◽

Solid Phase ◽

Internal Standard ◽

Enantiomeric Separation ◽

Rat Plasma ◽

Core Shell ◽

Chiral Hplc ◽

Phase Extraction ◽

Chiral Column ◽

Time Curve

A novel, fast and sensitive enantioselective HPLC assay with a new core–shell isopropyl carbamate cyclofructan 6 (superficially porous particle, SPP) chiral column (LarihcShell-P, LSP) was developed and validated for the enantiomeric separation and quantification of verapamil (VER) in rat plasma. The polar organic mobile phase composed of acetonitrile/methanol/trifluoroacetic acid/triethylamine (98:2:0.05: 0.025, v/v/v/v) and a flow rate of 0.5 mL/min was applied. Fluorescence detection set at excitation/emission wavelengths 280/313 nm was used and the whole analysis process was within 3.5 min, which is 10-fold lower than the previous reported HPLC methods in the literature. Propranolol was selected as the internal standard. The S-(−)- and R-(+)-VER enantiomers with the IS were extracted from rat plasma by utilizing Waters Oasis HLB C18 solid phase extraction cartridges without interference from endogenous compounds. The developed assay was validated following the US-FDA guidelines over the concentration range of 1–450 ng/mL (r2 ≥ 0.997) for each enantiomer (plasma) and the lower limit of quantification was 1 ng/mL for both isomers. The intra- and inter-day precisions were not more than 11.6% and the recoveries of S-(−)- and R-(+)-VER at all quality control levels ranged from 92.3% to 98.2%. The developed approach was successfully applied to the stereoselective pharmacokinetic study of VER enantiomers after oral administration of 10 mg/kg racemic VER to Wistar rats. It was found that S-(−)-VER established higher Cmax and area under the concentration-time curve (AUC) values than the R-(+)-enantiomer. The newly developed approach is the first chiral HPLC for the enantiomeric separation and quantification of verapamil utilizing a core–shell isopropyl carbamate cyclofructan 6 chiral column in rat plasma within 3.5 min after solid phase extraction (SPE).

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