Enantioselective HPLC-DAD method for the determination of etodolac enantiomers in tablets, human plasma and application to comparative pharmacokinetic study of both enantiomers after a single oral dose to twelve healthy volunteers

Hewala, Ismail I.; Moneeb, Marwa S.; Elmongy, Hatem; Wahbi, Abdel‐Aziz M.

doi:10.1016/j.talanta.2014.07.011

Cited by 19 publications

(7 citation statements)

References 32 publications

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“…Hewala et al . (), using a Kromasil® CelluCoat® chiral column, reported that resolution between the two enantiomers was 4.25 with the LOQs of ( R )‐etodolac and ( S )‐etodolac being 0.20 and 0.19 µg mL −1 , respectively. The LOQ by HPLC (Zorbax C 18 column) was 0.5 µg mL −1 for the diastereomers of ( RS )‐etodolac prepared with ( S )‐(−)‐ α ‐(1‐naphthyl)ethylamine ( S ‐NEA) (Jin et al ., ).…”

Section: Resultsmentioning

confidence: 99%

“…Hewala et al . () developed and validated an enantioselective HPLC method with diode array detection for determination of etodolac enantiomers in tablets and human plasma using a Kromasil® CelluCoat® chiral column (consisting of cellulose derivative for enantioselectivity). Nevertheless, chiral HPLC columns, for direct analysis, have high cost and relatively poor selectivity (Montes‐Bayón et al ., ).…”

Section: Introductionmentioning

confidence: 99%

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A novel approach for enantioseparation as applied to (RS)‐etodolac from pharmaceutical formulations: LC MS and density functional theory support for confirmation of diastereomers so separated

Singh

Bhushan

2015

Biomedical Chromatography

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In the present studies formation of diastereomers of (RS)-etodolac was confirmed using LC-MS when [M + H](+) or [M](+) were recorded for the diastereomers. The lowest energy optimized structures of two diastereomers were drawn, which confirmed the three-dimensional geometry of the diastereomers. This supports the optimized analytical separation conditions. In addition, separation of diastereomers was successful using a C18 column and a binary mixture of methanol and triethyl ammonium phosphate buffer of pH 4.5 (80:20, v/v) as mobile phase at a flow rate of 1 mL min(-1) and UV detection at 223 nm. The separation method was validated as per International Conference on Harmonization guidelines. (RS)-Etodolac was isolated from commercial tablets and purified and characterized to be used as racemic standard. Three pairs of diastereomers were synthesized using enantiomerically pure amines, namely, (R)-(+)-α-methyl benzyl amine, (S)-(-)-α,4-dimethylbenzylamine and (R)-(-)-1-cyclohexylethylamine. Derivatization reactions were carried out under conditions of stirring at room temperature (30 °C for 2 h) as well as under microwave irradiation (MWI), and the two types of diastereomers were compared. Reaction conditions for derivatization were optimized with respect to mole ratio of chiral derivatizing agent and (RS)-etodolac and MWI time. No racemization was observed throughout the study.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A novel approach for enantioseparation as applied to (RS)‐etodolac from pharmaceutical formulations: LC MS and density functional theory support for confirmation of diastereomers so separated

Singh

Bhushan

2015

Biomedical Chromatography

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“…The stability was assessed by comparing the mean concentrations of the stability sample with theoretical concentrations. The samples were considered stable if the assay results were within acceptable accuracy (100 ± 10%) .…”

Section: Methodsmentioning

confidence: 99%

Development and validation of a generic liquid chromatographic method for the simultaneous determination of five commonly used antimalarial drugs: Application to pharmaceutical formulations and human plasma

Mannemala

Nagarajan

2015

J of Separation Science

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A simple, sensitive, and rapid liquid chromatographic method was developed and validated using diode array detection for the determination of five commonly used antimalarial drugs in pharmaceutical formulations and in human plasma. Chromatographic separation of antimalarial drugs and internal standard (ibuprofen) was achieved on a C18 column with a mobile phase composed of 10 mM dipotassium orthophosphate at pH 3.0, methanol, and acetonitrile in a ratio of 20:38:42 v/v, at a flow rate of 1 mL/min. The analytes were monitored at 220 nm and separated in ˂10 min. The method was validated for linearity, accuracy, precision, limit of quantification, and robustness. Both intra- and interday precisions (in terms of %RSD) were lower than 3% and accuracy ranged from 98.1 to 104.5%. Extraction recoveries were ≥96% in plasma. The limits of quantitation for artemether, lumefantrine, pyrimethamine, sulfadoxine, and mefloquine were 0.3, 0.03, 0.06, 0.15, and 0.15 μg/mL in human plasma. Stability under various conditions was also investigated. The method was successfully applied for quantification of antimalarial drugs in marketed formulations and in spiked human plasma. The method can be employed for routine QC purposes and in pharmacokinetic investigations.

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“…High performance liquid chromatography (HPLC) is by far the most important tool used in the assessment of these parameters. The HPLC methods for etodolac, a nonsteroidal drug (NSAID) used in humans and domestic animals due to its analgesic, antipyretic and antiinflammatory effects, [3] described in literature are mostly used for its determination in tablets [4,5] , human plasma [3,6,7] and in river waters [8] . To the best of our knowledge there are no reports that describe the HPLC monitoring of conversion of 7-ethyltryptophol (7-ET) to etodolac methyl ester (EME), the main precursor in etodolac synthesis, over time on any scale.…”

Section: Introductionmentioning

confidence: 99%

HPLC Monitoring of Acid Catalyzed Conversion of 7-Ethyltryptophol to Methyl Ester of Etodolac

Habinovec¹,

Car²,

Ribić³

et al. 2016

Croat. Chem. Acta

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Small scale experimental model for the preparation of methyl ester of etodolac, the key intermediate in the synthesis of nonsteroidal drug etodolac, is thoroughly investigated in order to define the key parameters needed for its large scale production. Oxa-Pictet-Spengler reaction of 7-ethyltryptophol and methyl 3-oxopentanoate with inorganic acids as catalysts was monitored over time using HPLC method with UV detection. HPLC method for the simultaneous determination of 7-ethyltryptophol and the product was developed first. The conversion of 7-ethyltryptophol to etodolac precursor was performed using different molar equivalents of acid (1-5 with respect to the β-ketoester) and starting 7-ethyltryptophol of different degrees of purity. Kinetic profiles and optimal reaction times were in each case defined and key parameters selected.

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Enantioselective HPLC-DAD method for the determination of etodolac enantiomers in tablets, human plasma and application to comparative pharmacokinetic study of both enantiomers after a single oral dose to twelve healthy volunteers

Cited by 19 publications

References 32 publications

A novel approach for enantioseparation as applied to (RS)‐etodolac from pharmaceutical formulations: LC MS and density functional theory support for confirmation of diastereomers so separated

A novel approach for enantioseparation as applied to (RS)‐etodolac from pharmaceutical formulations: LC MS and density functional theory support for confirmation of diastereomers so separated

Development and validation of a generic liquid chromatographic method for the simultaneous determination of five commonly used antimalarial drugs: Application to pharmaceutical formulations and human plasma

HPLC Monitoring of Acid Catalyzed Conversion of 7-Ethyltryptophol to Methyl Ester of Etodolac

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