More than 50 million people worldwide do suffer from epilepsy, which is considered to be the most common neurological disorder. Epilepsy is defined as a spontaneous recurrence of unprovoked seizures, which can be treated with anti-epileptics drugs (AEDs) such as lacosamide (LCM), lamotrigine (LTG), levetiracetam (LEV), topiramate (TPM) and zonisamide (ZNS), and the treatment monitored with therapeutic drug monitoring (TDM) generally based on total plasma concentrations. During our research work, a procedure of ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) developed at Laboratory of Clinical Pharmacology in CHUV for the TDM of the five AEDs was adapted to quantify the free (unbound) plasma and salivary levels.