Analysis and stability study of temozolomide using
Authors: Melinda Andrasi, Rose Bustos, Attila Gaspar*, Frank A.
Gomez, Almos Klekner
Temozolomide is an oral anticancer medication that readily crosses the
blood brain barrier and can be used for the treatment of malignant
primary brain tumors. This pro-drug is hydrolyzed at physiologic pH
to the active component,
3-methyl-(triazen-1-yl)imidazole-4-car-boxamide (MTIC), and the
degradation product, 5-amino-imidazole-4-carboxamide (AIC), a highly
reactive cation. The positively charged AIC will methylate guanines
in DNA and cause a base pair mismatch. After failed attempts of the
cell to repair the mismatch, breaks of the daughter strand DNA will
occur and the cell will undergo apoptosis.
Analysis of Temozolomide concentration in patient serum has been
limited to High Performance Liquid Chromatography (HPLC) techniques.
Over the past 20 years, Capillary electrophoresis (CE) has emerged as
an effective and versatile separation tool for several reasons. CE
allows for detection of minute quantities of drugs in complex
biological matrices, at high resolution. To date, no detailed study
had been performed that used CE to analyze the serum concentrations of
Temozolomide and its degradants. The aim of our work was to study the
effectiveness for the simultaneous determination of Temozolomide, MTIC
and AIC in serum and brain tissue samples using capillary