Detection of a mixed-backbone oligonucleotide (GEM 231) in liver and tumortissues by capillary electrophoresis

A simple, rapid and sensitive method has been developed and validated for t he analysis of a mixed-backbone oligonucleotide (GEM 231) in tumor tissues. The analysis was performed using a capillary electrophoresis (CE) system w ith UV detection. An extended light path (bubble cell) capillary column of 64.5 cm (effective length 56 cm)x50 mum I.D. is used as the separation colu mn. The optimized chromatographic conditions were background electrolyte: s odium berate buffer (60 mM, pH 9.1), electrokinetic injection: 10 s, applie d voltage: 30 kV, detection at lambda =210 nm. A linear relationship was ob served between the peak area and the amount of GEM 231 in the range of 1.0- 1000 mug/ml. The lower detection limit of the drug was 100 pg with an avera ge recovery of about 75+/-5%. The inter-day and intra-day relative standard deviations were <10%. Assay validation studies revealed that CE method is reproducible and specific for the determination of GEM 231 in tissue homoge nates with a run time of less than 5 min. (C) 2001 Elsevier Science B.V. Al l rights reserved.