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This study reports a rapid and low‐cost LC method for control of enantiomeric purity of duloxetine. Though duloxetine, as marketed and administered, is expected to be a single (S)‐enantiomer, the analysis of a few commercial branded samples by the method developed and presented here showed that they contain a relatively high percentage of (R)‐enantiomer (e.g., 2.71–5.42%, which is undesirable in drug formulations). A new chiral derivatizing reagent [isatinyl‐(S)‐naproxen amide] was synthesized on (S)‐naproxen platform. Diastereomeric derivatives were synthesized under microwave irradiation and were separated using reversed‐phase‐HPLC on a C18 column. A combination of acetonitrile and triethylammonium phosphate buffer (9 mM, pH 4) as the mobile phase and detection at 273 nm were found successful. The diastereomeric derivatives at preparative scale were separated using open column chromatography, and the native enantiomers were obtained and characterized. The HPLC separation method was validated for detection limit, linearity, accuracy, and precision. The limits of detection of (S,R)‐diastereomer and (S,S)‐diastereomer were found to be 12 and 16 pg/mL, respectively, for the 20‐μL injected volume. The method so developed has a practical significance and greater societal impact in establishing the control of enantiomeric purity and in ensuring the enantiomeric purity of the drug meant for human consumption. [ABSTRACT FROM AUTHOR]

Abstract: Enantioselective analysis of (RS)‐fexofenadine was carried out by achiral HPLC via a derivatization approach using N‐hydroxy‐benzotriazolyl‐(S)‐naproxen ester (synthesized for this purpose) and three chirally pure amines as chiral derivatizing reagents. There occurred formation of amide and anhydride types of diastereomeric derivatives. These were separated and isolated by HPLC (analytical and preparative). The structures and configurations were verified via recording full‐scan product ion mass spectra using LC‐MS, 1HNMR spectra, Chem3D Pro 12.0 software and the software Gaussian 09 Rev.A.02 program and hybrid density functional B3LYP with 6‐31G basis set supplemented with polarimetry. Experimental conditions for synthesis and separations were optimized and the elution order was established. Analytical separation was performed on a C18 analytical column with different ratios of MeCN–TEAP buffer and MeOH–TEAP buffer (v/v) adjusted to pH 7.5 as mobile phase at a flow rate of 0.7 mL min‐1. Detection was performed via UV absorbance at 225 nm. The method was validated in accordance with International Conference on Harmonization guidelines. The detection limits were 6.25 and 7.87 ng mL‐1 for first and second eluting diastereomeric derivatives, respectively. [ABSTRACT FROM AUTHOR]

Atenolol, a β-adrenergic receptor antagonist, is a chiral compound used for the treatment of cardiovascular diseases and to treat hypertension, coronary heart disease, arrhythmias, sinus tachycardia and myocardial infarction, where it acts preferentially upon the β-adrenergic receptors in the heart. It is marketed as a racemate, but only the ( S)-enantiomer of ( RS)-atenolol is responsible for the β-adrenoceptor blocking activity. Different chromatographic methods have been applied for the separation and determination of enantiomers. In this article a review is presented on liquid chromatographic methods for enantioseparation of ( RS)-atenolol by both direct and indirect approaches involving practical applications of several chiral stationary phases, chiral derivatization reagents and ligand exchange and impregnation methods. These include methods using both HPLC and TLC for separation, determination and bioassay of enantiomers of atenolol. In addition, some aspects of enantioseparation under achiral phases of liquid chromatography have been briefly mentioned as applicable to ( RS)-atenolol. This review provides current available enantioseparation choices not only for ( RS)-atenolol but also for other applicable racemic drugs. [ABSTRACT FROM AUTHOR]

Baclofen is a commonly used racemic drug and has a simple chemical structure in terms of the presence of only one stereogenic center. Since the desirable pharmacological effect is in only one enantiomer, several possibilities exist for the other enantiomer for evaluation of the disposition of the racemic mixture of the drug. This calls for the development of enantioselective analytical methodology. This review summarizes and evaluates different methods of enantioseparation of ( RS)-baclofen using both direct and indirect approaches, application of certain chiral reagents and chiral stationary phases (though very expensive). Methods of separation of diastereomers of ( RS)-baclofen prepared with different chiral derivatizing reagents (under microwave irradiation at ease and in less time) on reversed-phase achiral columns or via a ligand exchange approach providing high-sensitivity detection by the relatively less expensive methods of TLC and HPLC are discussed. The methods may be helpful for determination of enantiomers in biological samples and in pharmaceutical formulations for control of enantiomeric purity and can be practiced both in analytical laboratories and industry for routine analysis and R&D activities. [ABSTRACT FROM AUTHOR]

An efficient, simple, validated, analytical and semi-preparative HPLC method has been developed for direct enantioresolution of ( RS)-Ketorolac (Ket) using monochloro-methylated derivatives of cellulose and amylose, i.e. cellulose (tris-3-chloro-4-methylphenylcarbamate) and amylose (tris-5-chloro-2-methylphenylcarbamate) as chiral stationary phases (CSPs) with photo diode array detection at 320 nm. Enantioresolution was carried out in samples of human plasma spiked with ( RS)-Ket under normal and reversed-phase elution modes with suitable mobile phase compositions. The effect of nature of alcohols (MeOH, EtOH, PrOH and n-BuOH) and other solvents (MeCN and MeOH) as organic modifiers in the mobile phase was investigated on the separation performance of two CSPs in terms of retention and separation of enantiomers. The best resolution was observed on cellulose-based CSP using EtOH, while using 2-PrOH (15%) and amylose-based CSP obtained the highest retention. Under reversed-phase elution mode the best enantioseparation was observed using 30% MeCN with ammonium formate buffer. The elution order of enantiomers was ascertained by determining specific rotations. The limit of detection and quantitation values were 5 and 15.5 ng/mL for each enantiomer of ( RS)-Ket, respectively. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Bupropion, a tricyclic aminoketone, is used primarily in the treatment of depression, the management of patients with bipolar and schizo-affective disorder, and the treatment of Parkinson's disease. Bupropion is marketed as a racemate, but the racemic mixture is known to have several disadvantages while the two isomers of bupropion and its metabolite differ significantly in their pharmacological activities. Therefore, the stereoselective determination of the drug enantiomers in pharamaceutical dosages, plasma or urine is of potential clinical and analytical importance. Different chromatographic methods have been employed for the separation of the two enantiomers. This is the first attempt to review the methods of enantiosepartion of bupropion using both direct and indirect approaches in both HPLC and TLC. The review presents a detailed discussion on the use of chiral stationary phase (based on polysaccharide, α1 acid glycoprotein and ovomucoid column) and chiral derivatizing reagents (based on isothiocyanate and cyanuric chloride) along with TLC separation of bupropion enantiomers using ligand exchange and impregnation methods. The focus is also on the separation mechanism for enantioresolution using the various methods described herein. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The present work reports preparative enantioseparation of ( RS)-baclofen using thin-layer chromatography (TLC) and high-performance (HPLC). Diastereomers were synthesized using a new monochloro-s-triazine-based chiral derivatizing reagent (CDR), namely, N-(4-chloro-6-piperidinyl-[1,3,5]-triazine-2-yl)-L-phenylalanine, under . Acetonitrile-0.1% aq. triflouroacetic acid in gradient elution mode and CH3OH-CH2Cl2 (4:5; v/v) were successful as mobile phase in HPLC and TLC, respectively. The two diastereomers were isolated by preparative TLC. Molecular dissymmetry was established by developing the lowest energy optimized structures of the diastereomers based on Density Functional Theory and with the help of 1H NMR showing anisotropic effect associated with aromatic ring of s-triazine (in the CDR). The configuration of diastereomers was established as [L-Phe-( R)-Bac] and [L-Phe-( S)-Bac], where the first notation refers to the configuration of chiral auxiliary (of the CDR) and the second to that of the analyte Bac. were found to be 0.056 and 0.061 ng mL−1, respectively, for the two diastereomers. Determination of absolute configuration of the two diastereomers lent support to the elution order and separation mechanism. Chirality 27:299-305, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Abstract: Two sulfur-containing amino acids, dl-cysteine (Cys) and dl-penicillamine (PenA), were condensed with ninhydrin to form their spirothiazolidine derivatives. These were separated by HPLC using α-acid glycoprotein (AGP) and β-cyclodextrin (β-CD) columns. The resolution conditions were optimized and the results were compared. Since the method provided resolution greater than 2 it was also applied to preparative separation. After separation, each of them was detagged using Zn dust and 10% aqueous trifluoroacetic acid. For analytical purposes dinitrophenyl (DNP) derivatives of dl-Cys and dl-PenA were also prepared and were resolved on both the columns. The detection was carried out using photodiode array detection system at 231nm. The limits of detection were found to be 0.01% and 0.004% for spirothiazolidine carboxylic acid and DNP derivatives, respectively. [Copyright &y& Elsevier]

A simple, sensitive and fast RPHPLC method was developed and validated for the enantioselective determination of (RS)‐isoprenaline (Ipn) in human plasma. The enantiomers were converted to diastereomeric derivatives using s‐triazine (cyanuric chloride) based chiral derivatizing reagents. l‐isoleucine and l‐methionine were introduced as chiral auxiliary in s‐triazine and two new monochloro‐s‐triazine reagents were synthesized. These reagents were characterized and used for synthesis of diastereomeric derivatives of (RS)‐Ipn spiked in human plasma. (RS)‐Ipn was isolated (purified and characterized) from a commercial pharmaceutical formulation and was used as the standard racemic sample. Structures of the two diastereomeric derivatives were optimized for lowest energy using the Gaussian 09 Rev A. 02 program and hybrid density functional B3LYP with 6‐31G* basis set which showed the spatial orientation of hydrophobic groups on stereogenic centers in the diastereomeric derivatives. The results were correlated with the mechanism of separation and elution order. Limit of detection values were found to be 24.6 and 26.8 ng mL−1 for the first and second eluting diastereomeric derivatives, respectively. [ABSTRACT FROM AUTHOR]

Propranolol, a β‐adrenergic receptor antagonist, is a chiral compound that is marketed as a racemate, but only the (S)‐(−)‐enantiomer is responsible for the β‐adrenoceptor blocking activity. Different chromatographic methods have been applied for separation and determination of enantiomers of (RS)‐propranolol. In this article a review is presented on different liquid chromatographic methods used for enantioseparation of (RS)‐propranolol, using both HPLC and TLC. In addition, some aspects of enantioseparation under achiral phases of liquid chromatography have been briefly mentioned. [ABSTRACT FROM AUTHOR]