Determination of four antiepileptic drugs in plasma using ultra‐performance liquid chromatography with mass detection technique

Abstract

Status epilepticus (SE) is considered the second most frequent neurological emergency. Its therapeutic management is performed using sequential antiepileptic drug regimens. Diazepam (DIA), midazolam (MID), phenytoin (PHT) and phenobarbital (PB) are four drugs of different classes used sequentially in the management of SE. A sensitive, selective, accurate and precise method was developed and validated for simultaneous determination of the four antiepileptic drugs in human plasma. Their separation and quantification were achieved using ultra-performance liquid chromatography (UPLC) with mass detection using carbamazepine as internal standard (IS). For the first three drugs and the IS, UPLC-MS/MS with electrospray ionization working in multiple reaction monitoring mode was used at the following transitions: m/z 285 → 193 for DIA; m/z 326 → 291 for MID; m/z 253 → 182 for PHT; and m/z 237 → 194, 237 → 192 for IS. For the fourth drug (PB), a molecular ion peak of PB [M + H] at m/z 233 was used for its quantitation. The method was linear over concentration ranges 5-500 ng/mL for DIA and MID and 0.25-20 μg/mL for PHT and PB. Bioanalytical validation of the developed method was carried out according to European Medicines Agency guidelines. The developed method can be applied for routine drug analysis, therapeutic drug monitoring and bioequivalence studies.

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“…17 Another detailed definition was given by the Epilepsy Foundation of America specifying a condition, where two or more consecutive seizures happen with loss of consciousness between them, or a persistent seizure that lasts for more than 30 minutes, as status epilepticus (SE). 18 The WHO states that epilepsy causes a major public health concern because it is an important cause for mortality and morbidity around the world. Also, population-based studies show that SE is considered the second most frequent neurologic emergency associated with high annual occurrence that increases almost logarithmically with age.…”

“…Also, population-based studies show that SE is considered the second most frequent neurologic emergency associated with high annual occurrence that increases almost logarithmically with age. 18,19 Prevalence studies of neurological disorders showed high rates of epilepsy in Arab countries including Egypt, Saudi Arabia and Lebanon, yet very few published studies evaluate the situation in these countries.…”