Two dimensional reversed-phase–reversed-phase separations

Gray, Michael J.; Dennis, Gary R.; Wormell, Paul; Shalliker, R. Andrew; Slonecker, Patrick J.

doi:10.1016/s0021-9673(02)01221-9

Cited by 67 publications

(46 citation statements)

References 34 publications

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“…This was expected since the BGE was the sole variable in the CZE methods, as opposed to the mobile and stationary phases being varied in the HPLC methods. Gray et al have reported similar HPLC results for the evaluation of comprehensive 2-D systems, with C values being comprised between 0.26 and 0.99, and between 0.45 and 0.64 for the separation of 32 isomers [3] and 58 oligostyrenes [17], respectively. In this study, the possibility of an improved degree of orthogonality for this set of analytes using CZE and HPLC selected methods was examined.…”

Section: Hplc Vs Hplc Orthogonalitymentioning

confidence: 80%

“…Hence, strategies to improve the throughput of analytical methods applied to impurity profiling of drug candidates have the potential to save time and produce safer and purer batches of drugs for initial biological evaluation. Automation of the method development stage is unlikely to solve the problem since it is accepted that the complete resolution of component peaks in complex samples is not practically feasible using a single separation method [3]. For example, Giddings [4] predicted that approximately four million theoretical plates would be required to separate 82 of 100 components randomly distributed in a single separation, which is clearly not feasible.…”

Section: Introductionmentioning

confidence: 99%

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A generic approach to the impurity profiling of drugs using standardised and independent capillary zone electrophoresis methods coupled to electrospray ionisation mass spectrometry

et al. 2005

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Three standardised, capillary zone electrophoresis-electrospray ionisation mass spectrometry (CZE-ESI-MS) methods were developed for the analysis of six drug candidates and their respective process-related impurities comprising a total of 22 analytes with a range of functional groups and lipophilicities. The selected background electrolyte conditions were found to be: 60/40 v/v 10 mM ammonium formate pH 3.5/organic, 60/40 v/v 10 mM ammonium acetate pH 7.0/organic and 10 mM piperidine, pH 10.5, where the organic solvent is 50/50 v/v methanol/acetonitrile. The coaxial sheath flow consisted of either 0.1% v/v formic acid in 50/50 v/v methanol/water, or 10 mM ammonium acetate in 50/50 v/v methanol/water, depending on the mixture being analysed. Factor analysis and informational theory were used to quantify the orthogonality of the methods and predict their complementarities. The three selected CZE-ESI-MS methods allowed the identification of 21 out of 22 of all the drug candidates and their process-related impurities and provided orthogonality with four established high-performance liquid chromatography-mass spectrometry (HPLC-MS) methods. These methodologies therefore form the basis of a generic approach to impurity profiling of pharmaceutical drug candidates and can be applied with little or no analytical method development, thereby offering significant resource and time savings.

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Section: Hplc Vs Hplc Orthogonalitymentioning

confidence: 80%

Section: Introductionmentioning

confidence: 99%

A generic approach to the impurity profiling of drugs using standardised and independent capillary zone electrophoresis methods coupled to electrospray ionisation mass spectrometry

et al. 2005

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“…A C18 column and methanol as the mobile phase in the first dimension and a ZRCarbon column and ACN in the second dimension were used for 2-D RP6RP separations of isotactic forms of oligostyrenes with various numbers of styrene units and various alkyl end-groups, where the carbon-clad zirconia column provides the separation of diastereoisomers, whereas the C18 column resolves the species with various numbers of styrene units and alkyl lengths. Even though the separation selectivities were strongly correlated, up to 30 species could be resolved using fractionation-reinjection [123][124][125] or the heart-cutting [126] approach. This approach was adapted for comprehensive separation of isomers in a mixture of oligostryrenes [127][128][129].…”

Section: Sec6np Sec6rp and Rp6np 2-d Separations Of Synthetic Polymmentioning

confidence: 99%

Column selectivity for two‐dimensional liquid chromatography

Jandera¹

2006

J of Separation Science

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Selectivity of phase system is of primary concern when designing a 2-D separation, as it affects the 2-D system orthogonality and consequently the peak capacity controlling the number of peaks that can be separated in the available 2-D retention space limited by the time of analysis. Possibilities for characterization of LC phase system selectivity with respect to different polar and nonpolar structural units are compared, with special attention to multidimensional samples with various types of repeat groups, such as homopolymers, (co)polymers, fatty acid esters with various acyl lengths and number and position of double bonds, etc. Possibilities of the 2-D LC separations of these and other sample types, including pharmaceuticals, natural phenolic compounds, biopolymers, etc., using various combinations of separation modes are reviewed. Rules for design of comprehensive 2-D LC x LC systems are discussed, with respect to mobile phase compatibility in the two systems and modulation techniques suppressing band broadening connected with the sample fraction transfer from the first to the second dimension. Pitfalls connected with online connection of normal-phase and RP LC systems and their possible practical solutions are addressed and illustrated by practical examples.

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“…Individual oligomer components for preparation of , unknowns' were isolated from each of these polystyrene standards using methods previously described [25]. A Phenomenex Luna C18 column (15064.6 mm, 5 lm particle diameter) (Phenomenex, Torrance, CA, USA) was used in the first separation dimension.…”

Section: Chemicalsmentioning

confidence: 99%

“…Since these samples were laboratory derived, we could produce a series of unknown compounds that we could then employ to test the fingerprinting capabilities of the 2-D LC system and be assured of the accuracy of the result since all components in the sample matrix were known. Extensive discussion on the separation of these compounds can be found in a number of related papers in this series of works [24][25][26][27]; suffice it to say that the oligomers and their subsequent isomeric forms elute according to molecular weight in the C18/methanol dimension. In the second dimension retention is highly dependent on structural orientation.…”

Section: Sample Descriptionmentioning

confidence: 99%

Multidimensional liquid chromatography for sample characterisation

Toups

Gray

Dennis

et al. 2006

J of Separation Science

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While LC finds enormously widespread use in almost all areas of chemical science, the technique is limited as a means of identification because compounds do not elute with unique retention times. This limitation spurred the growth of hyphenated instrumental methods of analysis, such as LC-MS/MS, which because of the MS/ MS detection became a method of identification. However, techniques like LC-MS/ MS are specialised and require high initial purchase and running costs, inhibiting the more widespread growth of the technique. In an attempt to increase the separation power of LC, multi-dimensional LC was developed. This expanded the separation space and subsequently has allowed the development of methods with fingerprinting ability due to the lower probability of component overlap. The work in this study illustrates the application of 2-D LC as a means of chemical fingerprinting. We employed a sample base of various low molecular weight oligostyrenes and their diastereomers that represent a population of compounds whose selectivities in a one-dimensional separation are almost unity and hence essentially impossible to separate. Yet in a 2-D domain almost all individual components occupy unique 2-D retention times.

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Two dimensional reversed-phase–reversed-phase separations

Cited by 67 publications

References 34 publications

A generic approach to the impurity profiling of drugs using standardised and independent capillary zone electrophoresis methods coupled to electrospray ionisation mass spectrometry

A generic approach to the impurity profiling of drugs using standardised and independent capillary zone electrophoresis methods coupled to electrospray ionisation mass spectrometry

Column selectivity for two‐dimensional liquid chromatography

Multidimensional liquid chromatography for sample characterisation

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