Roberto Mandrioli, Laura Mercolini, Maria Augusta Raggi, Ernst Kenndler, Nadia Ghedini, Mario Amore, Mandrioli R., Mercolini L., Ghedini N., Amore M., Kenndler E., and Raggi M.A.
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. 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. 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. 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.