Introduction: Topiramate (2,3:4,5-bis-O −(1-methylethylidene)-D-fructopyranose sulfamate) is one of the most recent anticonvulsant
agents introduced in the market. It seems to act as a sodium channel blocker and a
chloride channel activator, but its exact mechanism of action is still unclear. While
it is generally considered safer than other, older drugs (such as carbamazepine, valproate
or barbiturates), its use can still cause severe side effects: during chronic treatment,
patients can suffer from vision loss (glaucoma, myopia), osteoporosis, hyperthermia
and nephrolithiasis. In order to achieve optimal therapeutic efficacy and to reduce
the incidence of side and toxic effects, therapeutic drug monitoring (TDM) of patients
undergoing treatment with topiramate is clearly advisable. Methods: Two original methods were developed and compared for the TDM of topiramate: one based
on HPLC with fluorescence detection and one based on capillary electrophoresis (CE)
with indirect UV detection. Topiramate does not possess significant chromophores,
thus it has extremely low UV-visible absorbance and no spontaneous fluorescence. In
order to achieve sufficient sensitivity, the analyte was derivatised with dansyl chloride
before HPLC analysis, while indirect UV detection was implemented for CE, using sulfamethoxazole
as the absorbance probe. Results: Both analytical methods were fully validated. HPLC-F is somewhat more complicated
and time-consuming, due to the derivatisation procedure, but has also better precision
and extraction yields. It has also the advantage of allowing the determination of
other low-absorbing antiepileptics, such as gabapentin and vigabatrin. The CE method,
on the other hand, has the advantage of requiring much lower volumes of sample and
of expensive and polluting solvents. Conclusions: The methods have demonstrated to be suitable for the monitoring of patients undergoing
therapy with topiramate. They can be used alternatively, according to the needs of
the analysis and other considerations, such the potential for interference of other
co-administered drugs.
