QUANTITATIVE CAPILLARY GEL-ELECTROPHORESIS ASSAY OF PHOSPHOROTHIOATE OLIGONUCLEOTIDES IN PHARMACEUTICAL FORMULATIONS

Quantitative capillary gel electrophoresis (QCGE) has been developed f or the accurate quantitation of a 21-mer phosphorothioate oligonucleot ide, ISIS 2922, and its degradation products in an intravitreal formul ation. The electrokinetic mode of injection employed by CGE necessitat es formulation of the external reference standard in a sample matrix s imilar to that of the drug product and the use of an internal standard for improved accuracy and precision. The analytical method detailed i n this paper has demonstrated the necessary accuracy, precision, linea rity, range, selectivity and ruggedness for use in routine drug produc t analysis and stability monitoring of phosphorothioate oligonucleotid es.