Memory effect of diethylamine mobile phase additive on chiral separations on polysaccharide stationary phases

Abstract

The existence of a memory effect for amine additives on polysaccharide chiral stationary phases has often been suggested, but not clearly demonstrated. Demonstration of this effect is made difficult by the uncertainty as to which analytes benefit from use of amine additives and, typically, an unclear history of column use. In this work, analytes were selected for differences in their behavior with and without additives. Columns were used with no prior history. A persistent memory effect was demonstrated on a CHIRALPAK AD-H column in hexane-based mobile phases. This effect was short-lived, with polar organic mobile phases. Memory was short-lived on a CHIRALCEL OJ-H column. Flushing with isopropanol was shown to remove most of the memory effect. Compounds expected to require amine additives on CHIRALCEL OD-H column did not. Acid treatment of the AD-H and OD-H columns changed their performance, which was subsequently restored by the incorporation of amine.

Strategic use of preparative chiral chromatography for the synthesis of a preclinical pharmaceutical candidate

“…So-called memory effects with the use of amine modifiers with Chiralpak AD and similar stationary phases are well precedented. 12 In addition, as is often the case for enantioseparations carried out with very low modifier concentrations, small changes in modifier concentration were found to result in profound changes in chromatographic performance (Fig. 8A).…”

High‐Throughput Screening and Method Development Strategies to Separate Chiral Drug Compounds in HPLC, SFC, and CE

“…They are, for instance, used in polar organic solvent chromatography and normal-phase liquid chromatography: no aqueous buffers are applied in these mobile phases; thus, the ionization of the analytes is tuned by using organic acids and bases. Studies on mainly polysaccharide-derived CSPs have been made to investigate the effect of such acidic and basic additives on the chromatographic results [55,[68][69][70]. During these experiments a memory effect was noted: a phenomenon where these mobile-phase additives leave a trace on the chiral selector of the CSP.…”

“…The consequences of this contamination are that the separation results are affected. Stringham et al [69] did some experiments on polysaccharide-based stationary phases where the memory effect of DEA was clearly shown.…”

“…When it concerns apolar-type eluents (e.g., n-hexane based), the memory effect of DEA on the column lasts much longer than it does with polar organic eluents. Effective washing methods are derived from these findings: To minimize the memory effect of DEA, the column used should be washed with organic solvents and preferably with 2-propanol, which removes the basic additive memory effect almost completely [69]. The same suggestions are made by Matthijs et al [64].…”

The effect of acidic and basic additives on the enantioseparation of basic drugs using polysaccharide‐based chiral stationary phases

“…19 Recently, we reported that both acidic and basic mobile phase additives have significant effects on the enantioseparation of amino acids and their derivatives using one of the polysaccharide based CSPs, Chiralpak AD, as the chiral stationary phase. [20][21][22][23][24][25][26] Alkyl sulfonic acids and primary amines have been demonstrated to be better additives compared to the recommended trifluoroacetic acid and triethylamine and diethylamine. Acidic additives, such as ethanesulfonic acid, have been proven to be beneficial for the enantionseparation not only for acidic analytes, but also for basic analytes.…”