Development and validation of a chiral capillary electrophoresis method for assay and enantiomeric purity control of pramipexole

Abstract

A rapid method for the enantioseparation of pramipexole and its R-enantiomer has been developed by capillary electrophoresis. The influence of chemical and instrumental parameters was investigated including the type and concentration of chiral selectors, buffer composition and pH, co-ions, applied voltage, capillary length and temperature. Optimal separation conditions were obtained using a 50 mM phosphate buffer (pH 2.8) containing 25 mM carboxymethyl-β-cyclodextrin on a fused-silica capillary. Online UV detection was performed at 262 nm. A voltage of 25 kV was applied, and the capillary temperature was kept at 25°C. Hydrodynamic injection was performed at 3.45 kPa for 5.0 s. The separation of enantiomers was achieved in <6.5 min. The method was further validated in terms of stability of solutions, selectivity, linearity (both pramipexole and R-enantiomer, R(2) >0.995), LOD and LOQ (0.91 and 2.94 μg/mL, respectively), repeatability (RSD<1.5%) and accuracy (pramipexole, 100.4%; R-enantiomer, 100.5%). The proposed method was then applied to two kinds of pramipexole dihydrochloride monohydrate commercially available tablets, immediate release tablets (1.50 and 0.125 mg) and sustained release tablets (0.52 mg), to quantify the main component in the tablets. The amount of distomer could be quantified in bulk sample materials.

Impact of substituent position in monosubstituted α‐cyclodextrins on enantioselectivity in capillary electrophoresis

“…We ascertain that for all the studied analytes the chiral resolution decreased with an increasing pH and no separation of the individual enantiomers was achieved at pH 7 and 11 (data not shown). This finding was consistent with results published for carboxymethyl‐β‐CD derivatives and other anionic CDs used as the chiral additives in CE []. We obtained the chiral separations of the studied compounds only at pH 2.5 (Table ).…”

Recent advances in capillary electrophoretic migration techniques for pharmaceutical analysis

“…Only few report the use of electromigration techniques for the determination of the stereochemical purity of drug substances. Recent examples are summarized in Table . In the majority of the cases, LODs of 0.1% or below could be realized.…”

Recent advances in electrodriven enantioseparations

“…Therefore, the quality control of chiral drugs and their products involves also the determination of the unwanted stereoisomer (distomer) in the presence of the active stereoisomer (eutomer). During the reviewed period of time, several reports were published about the application of CE for the determination of enantiomeric purity and/or single active enantiomers in bulk drugs and/or final drug formulations including levocetirizine , ( R )‐modafinil , (–)‐huperzine A , ( R )‐pramipexol , ( R )‐(–)‐chloroquine , RS 86017 , L ‐methotrexate , ( S )‐pantoprazole , and escitalopram . The content of the lipoic acid enantiomers was determined in dietary supplements .…”