Determination of Carvedilol Enantiomers in Pharmaceutical Dosages by SBSE–HPLC Based on Diastereomer Formation

Abstract

A sensitive, selective and simple method for the simultaneous determination of carvedilol enantiomers in aqueous solution has been developed using stir bar sorptive extraction (SBSE) followed by high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection. This method is based on the reaction of carvedilol enantiomers with (-)-menthyl chloroformate (MCF) after extraction by the SBSE method to produce diastereomeric derivatives. The separation was achieved by use of a C18 analytical column and the influence of mobile phase composition on the enantioseparation of carvedilol was studied. The applicability of two sorptive phases, poly(methyl methacrylate/ethyleneglycol dimethacrylate) (PA-EG) and polydimethylsiloxane, were tested for extraction of carvedilol enantiomers from aqueous samples. The obtained results showed excellent linear dynamic ranges and precisions for each of them. The least limit of detection for (S)- and (R)-carvedilol obtained 8 and 11 µg L(-1), respectively, using the PA-EG sorptive phase. Inter- and intra-mean recoveries were also satisfactory, ranging from 98 to 103%, with coefficient of variation in the range of 1-5% at three fortified levels using a PA-EG coated stir bar. The proposed SBSE (PA-EG)-MCF derivatization-HPLC-UV method was successfully applied to enantioselective analysis of carvedilol in water and pharmaceutical dosages, confirming the application of this method.

RP‐HPLC enantioseparation of β‐adrenolytics using micellar mobile phase without organic solvents

“…The literature search revealed few reports for enantioseparation of ( RS )‐Cdl and ( RS )‐Sbl both by direct as well as indirect approaches of enantioseparation. Though certain efforts mentioned in a few reports were not successful for the separation of enantiomers of ( RS )‐Cdl and ( RS )‐Sbl (Ates, Mangelings, & Heyden, ; Bhushan & Dixit, ; Bhushan & Tanwar, ; Singh, Pallastrelli, & Miritello Santoro, ) and in a few cases enantiomers were resolved, but with a very low resolution (Ates et al, ; Hashema, Trundelberg, Attef, & Jira, ; Magiera, Adolf, & Baranowska, ; Moldovan, Dascăl, Mirel, Bodoki, & Oprean, ; Taraji et al, ). The results presented herein clearly show a better enantioresolution of ( RS )‐Bpl and ( RS )‐Bxl as compared with previous literature (Bhushan & Dixit, ; Moldovan et al, ).…”

Indirect enantioseparation of fluoxetine in mouse serum by derivatization with 1R‐(–)‐menthyl chloroformate followed by ultra high performance liquid chromatography and quadrupole time‐of‐flight mass spectrometry

“…Of the various CDRs available for reaction with secondary amines, MCF was selected for the chiral separation of fluoxetine in the present study because it has been widely used for indirect chiral separation of amine groups and because it forms stable diasteroisomers . MCF is commercially available in both R and S forms, and both forms have been used as CDRs in previous studies.…”

Solventless Microextration Techniques for Pharmaceutical Analysis: The Greener Solution

“…This could be related to the complexity of the biological matrix where SBSE is not a highly selective or specific extraction technique. Moreover, many pharmaceutical analytes are polar compounds, and they have reduced extraction efficiency when PDMS is in the stationary phase ( Camino-Sánchez et al, 2014 ; Taraji et al, 2015 ). Some approaches were carried out recently to increase the recovery of polar analytes, for instance, in situ derivatization and SBSE with solvent-swollen PDMS ( Ochiai et al, 2018 ).…”

“…SBSE was used to separate carvedilol enantiomers ( Taraji et al, 2015 ) in pharmaceutical dosage forms. The applicability of two sorptive phases, poly(methyl methacrylate/ethyleneglycol dimethacrylate) (PA–EG) and polydimethylsiloxane, was evaluated for extracting carvedilol enantiomers from aqueous samples.…”