Square‐Wave and Differential‐Pulse Adsorptive Stripping Voltammetry for Ultra‐Trace Determination of the Anti‐Angiogenic Drug Thalidomide in the Presence of Concomitant Drugs

Abstract

Adsorptive stripping differential‐pulse voltammetry (DPV) and square‐wave voltammetry (SWV) methods were developed, evaluated, and compared for ultra‐trace determination of thalidomide in pharmaceutical formulations and biological fluids (blood serum and urine). The most sensitive thalidomide reduction peak at −804 mV for SWV and at −921 mV for DPV were used. Selective pre‐concentration of thalidomide on the static mercury drop electrode (SMDE) was achieved, increasing the sensitivity of determinations. A study to verify potential interferences from concomitant active drugs, such as tetracycline and sulfanilamide, was performed. Strategies to allow selective determination of thalidomide in blood serum and urine are presented. Analytical figures of merit for both techniques are shown, with absolute limit of detection (ALOD), for 100 µL sample of 4.7 pg for DPV and 0.5 pg for SWV. Linear dynamic range extended over three and four orders of magnitude, respectively, for DPV and SWV. These methods were tested in a commercial pharmaceutical formulation and in two laboratory simulated tablets containing either sulfanilamide or tetracycline. Thalidomide spiked blood serum and urine were also analyzed, however, in these cases, sample pre‐treatment was necessary to minimize matrix interferences. Excellent recoveries were obtained for all samples analyzed.

Keywords:

• Thalidomide
• adsorptive stripping voltammetry
• biological fluids
• pharmaceutical formulations

The author acknowledges the financial support of FAPERJ‐Brazil (Grant E‐26 150.700/2003) and Dr. J. G. Aucélio for the donation of part of the substances employed in this work. C. E. Cardoso and R.O.R Martins acknowledge the financial support of CNPq, Brazil.