Unusual effect of column temperature on chromatographic enantioseparation of dihydropyrimidinone acid and methyl ester on amylose chiral stationary phase

Wang, Fang; O'Brien, Thomas P.; Dowling, Thomas M.; Bicker, G.; Wyvratt, Jean

doi:10.1016/s0021-9673(02)00404-1

Cited by 48 publications

(33 citation statements)

References 23 publications

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“…22 Chromatographic studies were complemented with IR, DSC, and solid-state NMR techniques in order to improve the understanding of the mechanism on a molecular level. 28,29,31 Solid-state NMR showed that 2-propanol was more effective in replacing hexane than ethanol. 29 A good correlation was observed for branched versus linear alcohols and elution order.…”

Section: Discussion On Enantioselective Mechanismmentioning

confidence: 99%

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Reversal of elution order for profen acid enantiomers in packed‐column SFC on Chiralpak AD

Gyllenhaal

Stefansson

2005

Chirality

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Enantiomeric separations of four 2-substituted propionic acid drugs have been studied using packed-column supercritical fluid chromatography (SFC) with amylose tris(3,5-dimethylphenylcarbamate) coated on silica as support (Chiralpak AD). Under standard conditions (i.e., flow rate, 1.5 ml/min; column temperature, 30 degrees C; back-pressure, 150 bar), the order of elution could be reversed when the polar alcohol modifier methanol in carbon dioxide was replaced by 2-propanol for ibuprofen, ketoprofen, and naproxen. For flurbiprofen, with the highest selectivity factor, no reversal was observed, although selectivity was reduced significantly with higher alcohols. Naproxen and flurbiprofen were also investigated with 2-butanol and 2-pentanol. The former showed reversal of elution order but not the latter. For higher alcohol modifiers, including 2-propanol, the peak symmetry was poor but could be improved by addition of citric acid in the alcohol modifier. These results stress the importance to investigate enantiomer elution order during the development of enantioselective methods and when chromatographic conditions are optimized. Preliminary experiments with column temperatures over the range of -15 to 45 degrees C revealed that, in a few cases, reversal took place with a change in temperature only.

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Section: Discussion On Enantioselective Mechanismmentioning

confidence: 99%

“…In a LC system with Chiralpak AD, Wang et al have seen much more serious thermally induced changes to the column with temperature. 28,29 Our experience is that, after sufficient re-equilibration, the column returns to its original state with perhaps some minor changes in retention.…”

Section: Other Alcohols and Modifiersmentioning

confidence: 99%

Reversal of elution order for profen acid enantiomers in packed‐column SFC on Chiralpak AD

Gyllenhaal

Stefansson

2005

Chirality

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“…IA and IB are the immobilized version of AD-H and OD-H phases. From our previous study [9], it was observed that the chromatographic behaviors of AD columns were affected by the column history. Therefore, the history for all the columns was carefully recorded in this study.…”

Section: Apparatus and Chromatographic Conditionsmentioning

confidence: 99%

“…However, understanding the potential for temperature-induced conformational changes on polysaccharide chiral stationary phases is critical for the optimization and reproducibility of enantiomer separations. Previous studies using a derivatized amylose phase (Chiralpak AD) equilibrated with ethanol (EtOH)/n-hexane (n-Hex) mobile phase demonstrated that temperature cycling created a path-dependant column behavior using dihydropyrimidinone (DHP) acid [9]. In that study the experiment was performed by first heating the columns from a starting temperature to an ending temperature (from 10 to 508C) by steps (usually, by 5 or 108C/step), and then cooling the columns by a stepwise procedure as the heating process.…”

Section: Introductionmentioning

confidence: 99%

“…At each given temperature, the column was equilibrated with the mobile phase(s) for 1 h before the measurement of retention factors of the probe compounds [10]. van't Hoff plots (constructed by plotting the logarithm of retention factors or selectivities versus the inverse of absolute column temperature) from the heating and cooling programs deviated from each other (hysteresis) [9,11,12]. From these studies, it was clear that the solvated AD phase underwent a thermally induced conformational transition once the temperature was above the transition point (around 308C).…”

Section: Introductionmentioning

confidence: 99%

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Column temperature programming in enantioseparation of dihydropyrimidinone compounds using derivatized cellulose and amylose chiral stationary phases

Wang¹,

Yeung²,

Han³

et al. 2008

J of Separation Science

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We report the application of column temperature programs as a tool to examine unusual temperature-induced behaviors of polysaccharide chiral stationary phases (CSPs). Using dihydropyrimidinone (DHP) compounds as probes we observed the heating (10-50 degrees C) and cooling (50-10 degrees C) van't Hoff plots of retention factors and/or selectivities of DHP compounds were not superimposable on AD, IA, and AS-H columns solvated with ethanol (EtOH)/n-hexane (n-Hex) mobile phases. The plots were not superimposable on AD, IB, and AS-H columns solvated with 2-propanol (2-PrOH)/n-Hex mobile phases. The thermally induced path-dependant behaviors were caused by slow equilibration as evidenced by the disappearance of the hysteresis in the second heating to cooling cycle and in a cooling to heating cycle. From the step-temperature program (10-50-10 degrees C), only EtOH solvated AD and AS-H phases showed the change of retention factors and/or selectivities with time while only 2-PrOH solvated AS-H phase showed similar behaviors.

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Temperature as a Variable in Pharmaceutical Applications

Smith

2006

HPLC for Pharmaceutical Scientists

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Unusual effect of column temperature on chromatographic enantioseparation of dihydropyrimidinone acid and methyl ester on amylose chiral stationary phase

Cited by 48 publications

References 23 publications

Reversal of elution order for profen acid enantiomers in packed‐column SFC on Chiralpak AD

Reversal of elution order for profen acid enantiomers in packed‐column SFC on Chiralpak AD

Column temperature programming in enantioseparation of dihydropyrimidinone compounds using derivatized cellulose and amylose chiral stationary phases

Temperature as a Variable in Pharmaceutical Applications

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