title: Simultaneous UPLC-MS/MS determination of antiepileptic agents for dose adjustment.
abstract: Therapeutic drug monitoring (TDM) of anti-epileptic drugs (AED) is a routine application. Carbamazepine (CRB) is monitored as the parent drug while oxcarbazepine (OXC) and eslicarbazepine acetate (ESL) are monitored as their active metabolite (eslicarbazepine; MHD). We have developed a UPLC-MS/MS method for determining CRB, OXC, ESL and MHD in plasma or serum with a simplified extraction protocol. The developed method detects sildenafil (SLD), which clinically interferes with AED and is likely to be co-administered in epileptic patients suffering from sexual insufficiency (60%). MHD was prepared in-house. AED were simultaneously determined in presence of SLD using gatifloxacin as an internal standard (IS). Separation was achieved using acetonitrile, methanol and 100 mm ammonium acetate in water (32:3:65, v/v/v) on an Intersil®RP-HPLC column (250 × 4.6 mm, 5 μm). A one-step extraction was performed by simultaneous protein and phospholipids precipitation. Detection was done by tandem mass spectrometry. No relative matrix effect was observed. The method was linear (0.5-40 μg/mL for CRB, ESL and MHD and 0.05-4 μg/mL for OXC), accurate and selective. Recoveries were 64.41 ± 5.07, 45.62 ± 1.73, 61.41 ± 4.77 and 60.33 ± 1.36 for CRB, OXC, ESL and MHD, respectively. The method was successfully applied for TDM of AED.
authors.affiliation: Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ahram Canadian University, 6th of October City, Egypt.
authors.forename: Faten
authors.initials: F
authors.lastname: Farouk
authors.affiliation: Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Ehab F
authors.initials: EF
authors.lastname: ElKady
authors.affiliation: Department of Chemistry, School of Science and Engineering, American University in Cairo, New Cairo, Egypt.
authors.forename: Hassan M E
authors.initials: HME
authors.lastname: Azzazy
mesh_terms: D000927:Anticonvulsants / Q000097:blood*; D002853:Chromatography, Liquid / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D057230:Limit of Detection; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000927:Anticonvulsants
keywords: anti epileptic drus; dose adjustment; drug-drug interaction; eslicarbazepine; oxcarbazepine; removal of phospholipids