Enantiomeric purity methods for three pharmaceutical compounds by electrokinetic capillary chromatography utilizing highly sulfated-gamma-cyclodextrin as the chiral selector

摘要

Methods for enantiomeric purity by electrokinetic chromatography were developed and validated for three pharmaceutical compounds, each utilizing highly sulfated-gamma-cyclodextrin (HS-gamma-CD) as the chiral recognition agent. Two of the compounds are weak bases, hence charged at low pH, and the third is a quaternary nitrogen compound, charged at all pH. In each instance quantification was via an authentic reference standard with addition of an internal standard. Separation was on a 61 cm x 50 mu m untreated capillary under reverse polarity with a background electrolyte of 5% HS-gamma-CD in pH 2.50 lithium phosphate buffer. Each method was validated with respect to the usual validation parameters, notably recovery and precision, yielding results, including limits of detection and quantitation, that allow reporting the minor enantiomer to 0.1% and less. In applying the methods, all batches of bulk drug tested were shown to be of enantiomeric purity >= 99.9%. (c) 2006 Elsevier B.V. All rights reserved.