Development of a validated capillary electrophoresis method for enantiomeric purity control and quality control of levocetirizine in a pharmaceutical formulation

Abstract

A chiral capillary electrophoresis method has been developed for the quantification of 0.1% of the enantiomeric impurity (dextrocetirizine) in levocetirizine and determination of both in pharmaceuticals using sulfated-β-cyclodextrins (CDs) as chiral selector. Several parameters affecting the separation were studied such as the type and concentration of chiral selectors, buffer composition and pH, organic modifier, mixtures of two CDs in a dual system, voltage, and temperature. The optimal separation conditions were obtained using a 50 mM tetraborate buffer (pH 8.2) containing 1% (w/v) sulfated-β-CDs on a fused-silica capillary. Under these conditions, the resolution of two enantiomers was higher than 3. To validate the method, the stability of the solutions, robustness (two level half fraction factorial design for 5 factors using 19 experiments [2(n-1)+3]), precision, linearity (dextrocetirizine 0.25-2.5 μg/ml, R(2) = 0.9994, y = 0.0375x + 0.0008; levocetirizine 15-100 μg/ml, R(2) = 0.9996, y = 0.0213x + 0.0339), limit of detection (0.075 μg/ml, 0.03% m/m), limit of quantification (0.25 μg/ml, 0.1% m/m), accuracy (dextrocetirizine 84-109%, levocetirizine 97.3-103.1%), filter effect, and different CD batches were examined. The validated method was further applied to bulk drug and tablets of levocetirizine.

Chiral selectors in CE: Recent developments and applications (2012‐mid 2014)

“…Deng et al. developed a chiral electrophoretic method for the quantification of 0.1% of the enantiomeric purity (dextrocetirizine) in levocetirizine by using sulfated‐β‐CDs (S‐β‐CD) as the CS. In their study, different other CSs, such as cellulose, dextran and heptakis‐(2,3‐diacetyl‐6‐sulfato)‐CD (HDAS‐β‐CD), were used and their performance was compared.…”

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 .…”

Advances in enantiomeric resolution on monolithic chiral stationary phases in liquid chromatography and electrochromatography

“…The United States Food and Drug Administration, European Committee for Proprietary Medicinal Products, Health Canada, Pharmaceutical and Medical Devices Agencies of Japan have banned the marketing of all racemic drugs . Chiral resolution is a great challenge for scientists and industrialists to separate and ensure optical purity of enantiomers . Most of the available chiral stationary phases are suitable for small to moderate molecular weight racemates but failed to give good chiral resolution of large molecules.…”