Analysis and stability study of temozolomide using capillary electrophoresis

Area of Science:

• Analytical Chemistry
• Pharmaceutical Analysis

Background:

• Temozolomide (TMZ) is a crucial chemotherapy agent.
• Accurate analysis of TMZ and its degradants is essential for therapeutic monitoring and stability studies.
• Existing analytical methods may lack speed or sensitivity for routine application.

Purpose of the Study:

• To evaluate the applicability of micellar electrokinetic capillary chromatography (MEKC) for the analysis of temozolomide (TMZ) and its primary degradants, 3-methyl-(triazen-1-yl)imidazole-4-carboxamide (MTIC) and 5-amino-imidazole-4-carboxamide (AIC).
• To develop a rapid and precise analytical method for TMZ quantification in biological matrices.
• To investigate the stability of TMZ under various conditions (pH, matrix).

Main Methods:

• Micellar electrokinetic capillary chromatography (MEKC) with short-end injection.
• On-capillary UV detection.
• Analysis of TMZ and its degradants (MTIC, AIC).
• Stability studies in aqueous solutions and serum at different pH values and room temperature.

Main Results:

• MEKC analysis of TMZ and its degradants achieved completion within 1.2 minutes.
• Excellent precision was obtained, with migration times better than 1.6% relative standard deviation (RSD).
• The limit of quantitation (LOQ) ranged from 0.31 to 0.93 microg/mL.
• Therapeutic concentrations of TMZ in blood samples were measurable after direct injection.
• TMZ exhibited a half-life of 33 minutes in serum at room temperature, comparable to 28 minutes in water at pH 7.9.

Conclusions:

• MEKC is a highly effective and rapid technique for the simultaneous analysis of temozolomide and its key degradants.
• The developed method offers high precision and sensitivity, suitable for therapeutic drug monitoring and stability assessments.
• TMZ demonstrates limited stability in aqueous and serum matrices, highlighting the importance of analytical monitoring.