Epilepsy is one of the oldest diseases known to man. For a long time there has not been a successful way of preventing epileptic seizures. At the beginning of the 20th century, phenobarbital, a drug that has been prescribed to induce sleep, has been proven to act as an anticonvulsant. Since then, many more drugs have been introduced. Thus, the need for therapeutic drug monitoring arose.
The goal is to keep drug concentrations at an optimal level and avoid drug toxicity by prescribing too high of a dose or undertreatment by prescribing lower doses. In this thesis we have validated a method of high performance liquid chromathography coupled with tandem mass spectrometry for determining the concentrations of 17 antiepileptic drugs: vigabatrine, pregabaline, gabapentine, levetiracetam, sulthiame, PEMA, zonisamide, rufinamide, felbamate, lacosamide, lamotrigine, 10-OH-carbamazepine, topiramate, brivaracetam, retigabine, perampanel and stiripentol.
Reference method for determining the concentration of many drugs, including antiepileptics is high performance liquid chromatography coupled with tandem mass spectrometry. This method ensures high accuracy and selectivity with less interferences than other methods. Chromatography techniques paired with mass spectrometry are steadily replacing immunochemical methods.
Our validation goal was to ensure that the method is adequate for routine use in medical laboratory. We have tested repeatability (CV<8,9%), accuracy (bias <11,5%) and selectivity. We have also determined linear ranges for all analytes (highest deviation from linearity was 14,7 %), level of blank (<2,5 mg/L), limit of detection (<3,4 mg/L), limit of quantification (<23,2 mg/L). We tested stability of control material under different conditions (deviation from true value <15 %), carryover (<17,3 %) and matrix effect (<105,4 %).
After the validation process, we have determined that the method is suitable for routine use in medical laboratory.
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