Comparative performances of selected chiral HPLC, SFC, and CE systems with a chemically diverse sample set

Borman, Phil J.; Boughtflower, Bob; Cattanach, Kaye; Crane, Kathleen; Freebairn, Keith; Jonas, Greg; Mutton, Ian M.; Patel, Asha; Sanders, Matt; Thompson, Duncan R.

doi:10.1002/chir.10260

Cited by 39 publications

(29 citation statements)

References 37 publications

(25 reference statements)

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“…SFC and CE offer potential advantages vis-à-vis HPLC and complement one another in terms of solubility options [1]. Although progress continues to be made in nonaqueous chiral CE [2,3], aqueous CE dominates the field of chiral CE analysis.…”

Section: Pha-543613 N-(3r)-1-azabicyclo[222]oct-3-ylfuro[23-c]-mentioning

confidence: 99%

Method for enantiomeric purity of a quinuclidine candidate drug by capillary electrophoresis

Ramstad¹,

Johnson

2006

J of Separation Science

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A chiral procedure based on EKC was developed and validated for determination of the enantiomeric purity of PHA-543613, a drug candidate that was under development for treatment of the cognitive deficits of Alzheimer's disease and schizophrenia. Separation of enantiomers is accomplished via differential, enantiospecific complexation with a single-isomer, precisely sulfated beta-CD and heptakis-6-sulfato-beta-CD (HpS-beta-CD). Both neutral and sulfated CDs were screened before selecting HpS-beta-CD as the chiral selector. The separation is conducted in a 61 cm x 50 microm uncoated fused silica capillary with 25 mM HpS-beta-CD in pH 2.50, 25 mM lithium phosphate as the separation buffer with detection at 220 nm. Application of reverse polarity at -30 kV results in an elution time of about 12 min for PHA-543613 and 13 min for the undesired S-enantiomer. Quantification is versus an authentic reference S-enantiomer as an external standard in combination with an internal standard. The procedure was validated over the range 0.1-2.0% w/w. The detection limit is 0.01-0.02%. The amount of distomer intrinsic to the drug substance is about 0.1% or less. The developed method was used to generate stability data on multiple lots: in one case for up to 3 years.

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Section: Pha-543613 N-(3r)-1-azabicyclo[222]oct-3-ylfuro[23-c]-mentioning

confidence: 99%

Method for enantiomeric purity of a quinuclidine candidate drug by capillary electrophoresis

Ramstad¹,

Johnson

2006

J of Separation Science

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“…As pointed out above, the 2-APAs are frequently used as "typical" acidic pharmaceuticals for an evaluation of novel separation techniques and/or approaches to enan-tiomeric resolution [88][89][90][91][92][93] and are included in compilations of resolutions using a variety of selectors [94]. It is therefore difficult to ensure that all the reported methodologies are covered in this review.…”

Section: Enantiomeric Resolution and Analysis Of 2-apa Nsaidsmentioning

confidence: 99%

Enantiomeric resolution of 2‐arylpropionic acid nonsteroidal anti‐inflammatory drugs by capillary electrophoresis: Methods and applications

Patel¹,

Hanna-Brown²,

Hadley³

et al. 2004

Electrophoresis

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The 2-arylpropionic acids (2-APAs) are an important group of nonsteroidal anti-inflammatory drugs. These agents, the majority of which are available as racemates, exhibit stereoselectivity in both their action and disposition. Developments in stereoselective separation science methodology, mainly chromatographic, have facilitated an evaluation of the pharmacological properties of the individual enantiomers of these drugs and contributed to our understanding of both their mode(s) of action and disposition. While a number of electrophoretic techniques, including capillary electrophoresis, capillary electrochromatography and isotachophoresis, have been applied to the stereoselective resolution and stereospecific analysis of these agents using a variety of chiral selectors, e.g., cyclodextrins, oligosaccharides, macrocyclic antibiotics, and proteins, the number of published applications in pharmaceutical and biomedical analysis remains relatively limited. However, the utility of electrophoretic techniques for stereospecific analysis may be illustrated using the 2-APAs as typical examples of chiral acidic pharmaceuticals. Applications include: determination of enantiomeric composition following biosynthetic stereoselective hydrolysis; examination of both achiral and chiral impurity profiles in bulk drugs and formulated products; determination of enantiomeric impurities in both bulk drugs and formulated products; examination of configurational stability following stress testing of formulated products; determination of enantiomeric composition and metabolite profile in biological fluids following administration of the racemates and individual enantiomers. It may be anticipated that future exploitation of electrophoretic approaches to the stereospecific analysis of these agents will result in further contributions to our understanding of their stereoselective biological properties and therapeutic use.

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“…[24] using a test set of 102 chiral molecules. More than 100 different systems were tested to evaluate the performance of the techniques.…”

Section: Separations On Polysaccharide-based Cspmentioning

confidence: 99%

Chiral separations in sub‐ and supercritical fluid chromatography

Mangelings

Heyden²

2008

J of Separation Science

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Comparative performances of selected chiral HPLC, SFC, and CE systems with a chemically diverse sample set

Cited by 39 publications

References 37 publications

Method for enantiomeric purity of a quinuclidine candidate drug by capillary electrophoresis

Method for enantiomeric purity of a quinuclidine candidate drug by capillary electrophoresis

Enantiomeric resolution of 2‐arylpropionic acid nonsteroidal anti‐inflammatory drugs by capillary electrophoresis: Methods and applications

Chiral separations in sub‐ and supercritical fluid chromatography

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