title: 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.
authors.affiliation: Katholieke Universiteit Leuven, Faculteit Farmaceutische Wetenschappen, Laboratorium voor Farmaceutische Analyse, Leuven, Belgium.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Deng
authors.forename: Bart
authors.initials: B
authors.lastname: De Cock
authors.forename: Ruud
authors.initials: R
authors.lastname: Vervoort
authors.forename: Dirk
authors.initials: D
authors.lastname: Pamperin
authors.forename: Erwin
authors.initials: E
authors.lastname: Adams
authors.forename: Ann
authors.initials: A
authors.lastname: Van Schepdael
mesh_terms: D002021:Buffers; D017332:Cetirizine / Q000032:analysis / Q000737:chemistry* / Q000302:isolation & purification*; D002626:Chemistry, Pharmaceutical; D019075:Electrophoresis, Capillary / Q000379:methods*; D005374:Filtration; D039563:Histamine H1 Antagonists, Non-Sedating / Q000032:analysis / Q000737:chemistry* / Q000302:isolation & purification*; D006863:Hydrogen-Ion Concentration; D057230:Limit of Detection; D016014:Linear Models; D011786:Quality Control; D013237:Stereoisomerism; D013607:Tablets; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D002021:Buffers; D039563:Histamine H1 Antagonists, Non-Sedating; D013607:Tablets; D047392:beta-Cyclodextrins; C400661:heptakis(2,3-dimethyl-6-sulfato)cyclodextrin; C472067:levocetirizine; D017332:Cetirizine