Liquid chromatography on triacetylcellulose

Rimböck, Karl-Heinz; Kästner, Fritz; Mannschreck, Albrecht

doi:10.1016/s0021-9673(01)81936-1

Cited by 31 publications

(5 citation statements)

References 11 publications

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“…These values indicate that interconversion of the two enantiomers is slow enough to prevent any thermal racemization at room and body temperatures. Chiral separation procedures based upon liquid chromatography [14,15] and capillary zone electrophoresis (CZE) [10] did reveal resolu- tion of the two MQ rotamers and the MQ enantiomers were shown to possess unequal anticonvulsant activities [7]. The existence of the two stable MQ conformers and their absolute configuration was determined by circular dichroism spectroscopy and CNDO/S calculated rotational strengths and the M-configuration could thereby be assigned to the (2)-enantiomer [9].…”

Section: Introductionmentioning

confidence: 99%

Assessment of the stereoselective metabolism of methaqualone in man by capillary electrophoresis

Prost

Thormann

2003

Electrophoresis

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Methaqualone (MQ) and its hydroxylated metabolites are quinazoline derivatives that exhibit atropisomerism. As a continuation of our previous work with these compounds (Electrophoresis 2001, 22, 3270-3280), chiral capillary zone electrophoresis with hydroxypropyl-beta-cyclodextrin as buffer additive and multiwavelength absorbance detection is shown to be an effective tool to provide insight into the stereoselectivity of the MQ metabolism. The five major monohydroxy MQ metabolites formed during biotransformation do not show enantiomerization at temperatures up to 85 degrees C. Enzymatic and acidic hydrolysis of urines that were collected after concomitant administration of 250 mg of MQ and 25 mg diphenhydramine (DH) chloride are both shown to provide stereoselective metabolic patterns with 4'-hydroxymethaqualone, the major urinary metabolite, being excreted almost exclusively as a single enantiomer. A stereoselectivity in the formation of 2'-hydroxymethaqualone and 2-hydroxymethaqualone was also observed in vitro using human liver microsomes and preparations containing the cytochrome P450 enzyme (CYP) CYP3A4 only. The presence of DH during incubation with human liver microsomes did not reveal a difference in the metabolic pattern obtained. Furthermore, CYP2D6 and CYP2C19 do not significantly contribute to the metabolism of MQ. This was independently observed in vitro and via analysis of urines of individuals that are either efficient metabolizer phenotypes or poor metabolizer phenotypes for the two polymorphic enzymes. Although interindividual differences in the monitored metabolic patterns were noted, no marked difference could be related to a CYP2D6 or CYP2C19 polymorphism.

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Section: Introductionmentioning

confidence: 99%

Assessment of the stereoselective metabolism of methaqualone in man by capillary electrophoresis

Prost

Thormann

2003

Electrophoresis

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“…synthesized at low cost, it is a material of choice for SMB chiral chromatography is, in this way, a preparative chromatographic applications [13]. Some promising technique for the preparative production semi-preparative and preparative chiral separations of single enantiomeric drugs able to compete to up to on cellulose triacetate have been reported in literanow dominating techniques such as elution batch ture [3,5,[14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Separation of enantiomers of a chiral epoxide by simulated moving bed chromatography

Pais

Loureiro

Rodrigues

1998

Journal of Chromatography A

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The paper deals with chiral separation by simulated moving bed (SMB) chromatography. The separation of chiral epoxide enantiomers in microcrystalline cellulose triacetate using methanol as eluent is considered as illustrative example. The use of microcrystalline cellulose triacetate for the chromatographic separation of enantiomers is first reviewed and a methodology for obtaining basic data (adsorption equilibrium isotherms, axial dispersion and mass transfer coefficient) is discussed. A model for the prediction of the cyclic steady-state performance of the SMB, based on the analogy with the true moving bed, is developed assuming multicomponent adsorption equilibria, axial dispersion flow and linear driving force approximation to describe the intraparticle mass transfer rate. The simulation package is used to predict the effect of operating variables on the process performance and to define the regions for enantiomer separation. A simple optimization procedure is proposed for choosing the best SMB operating conditions. This procedure is extensively tested for the separation of chiral epoxide enantiomers. The experimental operation of a SMB pilot unit was carried out for this system. Purities and recoveries higher than 90% were obtained for both extract and raffinate, using a 420 ml inventory of stationary phase. The SMB pilot allows the continuous resolution of 52 g of racemic mixture per day and per liter of bed, with a solvent consumption of 0.4 l of mobile phase per gram of racemic mixture processed. The simulation package is also used to predict the steady-state internal concentration profiles for the SMB operation with reasonable agreement with experimental results.

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“…Although the run elutes the second peak after ca. 20 h, this represents a considerable improvement over the work of Rimbock et al , 3 who obtained only 7% purity of the first peak for a 1 g loading of TFAE racemate on a 243 x 40 mm column operated at 100 pm s-'.…”

Section: Resultsmentioning

confidence: 55%