Chiral drugs: An industrial analytical perspective

Wozniak, Timothy J.; Bopp, Ronald J.; Jensen, Eric C.

doi:10.1016/0731-7085(91)80160-b

Cited by 55 publications

(29 citation statements)

References 12 publications

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“…The main advantage of using direct methods involving chiral stationary phases (CSPs) is that derivatization is usually not required. Direct separation of drug enantiomers in biological fluids using CSPs frequently shows good selectivity between enantiomers but the chromatographic conditions tend to be fairly restricted and the presence of co-extracted endogenous contami-nants and/or trace impurities may have marked effects on resolution and column stability [41,42]. Separation of ibuprofen enantiomers in plasma on an (xl-acid glycoprotein CSP, using both isocratic and gradient elution, has been reported [15][16][17] but poor sensitivity and batch to batch variability in the stationary phases may limit the utility of the method.…”

Section: Introductionmentioning

confidence: 99%

Enantiospecific analysis of ibuprofen by high performance liquid chromatography: Determination of free and total drug enantiomer concentrations in serum and urine

et al. 1997

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SummaryA reversed-phase high-performance liquid chromatographic (HPLC) assay, based on the indirect approach to enantiomeric analysis, for the determination of ibuprofen in human serum and urine has been developed. Following the addition of (R,S)-flurbiprofen, as internal standard, the enantiomers of ibuprofen were isolated from plasma and urine samples by liquid-liquid extraction at acidic pH. The enantiomers of flurbiprofen and ibuprofen were derivatized with (R)-l-(naphthen-1-yl)ethylamine, using 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and 1-hydroxybenzotriazole as coupling reagents, to yield the corresponding diastereoisomeric amides. Chromatographic resolution of the derivatives was achieved using a C18 column (Waters Resolve C18; 5 gin, 150 x 3.9 mm) using a mobile phase of phosphate buffer (pH 3.5, 0.01 M): acetonitrile (50:50 v/v) at a flow rate of 1.5 mL min -1 at ambient temperature. Quantification was carried out using a spectrofluorometer with excitation and emission wavelengths of 290 and 330 nm respectively. The use of a semimicrobore column (150 x 2.1 mm) containing the same stationary phase facilitated the analysis of the free drug enantiomer concentrations following equilibrium dialysis. The derivatization procedure was carried out as described above but with a reduction in the quantities of the reagents used in order to reduce the background noise in the chromatographic analysis. The HPLC methodology for the determination of free drug enantiomer concentrations was validated against a previously reported method employing the radiolabelled drug.

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Section: Introductionmentioning

confidence: 99%

Enantiospecific analysis of ibuprofen by high performance liquid chromatography: Determination of free and total drug enantiomer concentrations in serum and urine

et al. 1997

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“…Fig. 6 Electropherograms of a mixed standard solution (1) and commercial Zoloft tablet of sertraline (2). The others were the same as in Fig.…”

Section: Discussion On Separation Mechanismmentioning

confidence: 99%

“…2,3 Microemulsion electrokinetic chromatography (MEEKC), one kind of improved CE methods that employs a surfactant in the background electrolyte, had been proposed as a useful technique for chiral analysis. 4,5 So far, MEEKC had been widely used in the separation of drug enantiomers as well an isomers.…”

Section: Introductionmentioning

confidence: 99%

Chiral Separation of Sertraline with Microemulsion Electrokinetic Chromatography on a Polymer/β-cyclodextrin Assembling Molecular Film Modified Capillary

Zhang

Tu³

2010

ANAL. SCI.

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A capillary modified by assembling a molecular film was presented for the chiral separation of sertraline by microemulsion electrokinetic chromatography. The assembling molecular film was constructed with poly(diallyldimethylammoniumchloride) and β-cyclodextrin via inclusion complexation. The separation efficiency of cis-trans isomers and enantiomers of sertraline was improved with a running microemulsion that contained the acetonitrile, sodium dodecyl sulfate, n-butanol and n-hexane buffered with sodium tetraborate. The baseline separation of four sertraline cis-trans isomers and enantiomers was achieved under the optimum conditions. The detection limit for isomers and enantiomers of sertraline (1S,4S, 1R,4R, 1S,4R, 1R,4S) was 0.15, 0.15, 0.30, 0.30 mg/L, respectively. The mechanism of chiral separation was studied and it could be applied for the determination of commercial Zoloft tablet samples satisfactorily.

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“…For drugs that contain one or more stereogenic centers, the chiral purity may be an important component in the determination of purity and stability. A variety of chiral assay techniques are available to the analyst including nuclear magnetic resonance (NMR), infrared spectroscopy (IR), gas and liquid chromatography (GC and LC), thin-layer chromatography (TLC) and recently, capillary electrophoresis (CE) [1].…”

Section: Introductionmentioning

confidence: 99%

Stereoselective determination of S-naproxen in tablets by capillary electrophoresis

Fillet

Fotsing

Bonnard

et al. 1998

Journal of Pharmaceutical and Biomedical Analysis

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A capillary electrophoresis (CE) method was developed for the stereoselective determination of the non-steroidal anti-inflammatory drug (NSAID), S-naproxen, in tablets. Several i-cyclodextrin derivatives (CDs) were tested as chiral selectors, including sulfobutyl-i-CD (SBCD), carboxymethyl-i-CD (CMCD), dimethyl-i-CD (DMCD) and trimethyl-i-CD (TMCD), in a phosphoric acid/triethanolamine pH 3 buffer. Under these conditions, the analyte was mainly present in an uncharged form and therefore, the use a neutral CD (DMCD or TMCD) alone could not lead to enantiomeric separation. On the contrary, by addition of a charged CD (SBCD or CMCD) to the running buffer, giving the analyte enantiomers an adequate mobility, chiral resolution could be achieved, although the resolution values obtained in this case were not quite satisfactory (RsB 1.5). Dual systems, based on the use of mixtures of charged and neutral CDs, were then investigated. The SBCD/TMCD system was found to be particularly well suited to the enantioseparation of naproxen and after optimisation of the concentrations of both CDs, a resolution value of 5.4 could be obtained. The method was validated for the determination of R-naproxen (enantiomeric impurity) in the 0.1-2% range, using the racemic mixture of the analyte. A second validation was performed in the 50 -150% range for the quantitation of S-naproxen. In both cases, good results with respect to linearity, precision and accuracy were obtained.

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Chiral drugs: An industrial analytical perspective

Cited by 55 publications

References 12 publications

Enantiospecific analysis of ibuprofen by high performance liquid chromatography: Determination of free and total drug enantiomer concentrations in serum and urine

Enantiospecific analysis of ibuprofen by high performance liquid chromatography: Determination of free and total drug enantiomer concentrations in serum and urine

Chiral Separation of Sertraline with Microemulsion Electrokinetic Chromatography on a Polymer/β-cyclodextrin Assembling Molecular Film Modified Capillary

Stereoselective determination of S-naproxen in tablets by capillary electrophoresis

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