Separation and determination of chiral composition in penicillamine tablets by capillary electrophoresis in a broad pH range

Abstract

A chiral capillary electrophoretic method with nearly full pH window was explored for the separation and determination of dl-penicillamine. A facile one-pot labeling technique was coupled in the method for introduction of chromophore and charge groups onto the analytes to facilitate the electromigration and sensitive detection. By using simply a cost-effective neutral β-cyclodextrin as chiral selector, baseline separation of the dl-penicillamine was achieved from pH 2.0 to over pH 10. Quantification of standard d- and l-penicillamines was demonstrated by taking pH 4.5, 7.4, and 9.7 as the representatives of acidic, neutral, and basic conditions. The working curves were constructed between peak area and concentration, having linear ranges of 8.56-8.56 × 10(2) μg/mL for pH 4.5 and 8.56-1.71 × 10(3) μg/mL for pH 7.4 and 9.7, with correlation coefficients all better than 0.999. The limit of detection (S/N = 3) was 2.58 μg/mL in acidic and neutral conditions or 1.41 μg/mL in basic condition. The method was further validated by assaying the commercial penicillamine tablets, applicable to quantification of the effective enantiomer and the trace impurity of l-penicillamine at a content of down to 0.2, 0.6, and 2.0% for pH 9.7, 4.5, and 7.4, respectively. The recovery determined by spiking technique was in a range from 93.1 to 105 %. The method is easily extendable to the analysis of other chiral amines or amino acids.

Application of cyclodextrins in chiral capillary electrophoresis

“…This also implies that the number of substituents on each glucose unit is unknown. Nevertheless, these randomly substituted CDs can be very useful in enantioseparations because their separation ability is different from single isomers . Sometimes, the migration order of enantiomers can be reversed as a consequence of the change of the degree of substitution .…”

Capillary electrophoresis in the analysis of biologically important thiols

“…Song et al. applied a one pot technique with cyanuric chloride and 7‐amino‐1,3‐naphthalenedisulfonic acid monopotassium salt for derivatization and subsequent chiral separation of PENA in commercial tablets. As the chiral separation is quite important with this type of drug, Min et al.…”

New approaches in sensitive chiral CE

“…Two methodologies used 7‐aminonaphthalene‐1,3‐disulfonic acid (ANDA) , while FITC and d ‐alanilol were selected as chromogenic reagents in other two works. Ribose and penicillamine were derivatized with ANDA in biocatalytic reaction solution and pharmaceutical tablets, respectively, obtaining LODs of 7 × 10 −7 M for ribose, and 9 × 10 −7 M for penicillamine. On the other hand, FITC as chromogenic reagent has gained attention for the sensitivity enhancement that can be achieved with LIF detection due to the highly fluorescent derivatives generated.…”