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

• DOI: 10.1002/bmc.4253
• Publication Date: 2018-04-11T00:45:25Z
• Authors: Sonia T. Hassib; Hanaa M.A. Hashem; Marianne A. Mahrouse; Eman A. Mostafa
• Keywords: Therapeutic Drug Monitoring; Bioanalysis; Bioequivalence; MicroDose; Phenobarbital

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