title: Robust isocratic high performance liquid chromatographic method for simultaneous determination of seven antiepileptic drugs including lamotrigine, oxcarbazepine and zonisamide in serum after solid-phase extraction.
abstract: A rapid, simple and robust method is presented for the simultaneous determination of seven antiepileptic drugs (AEDs), including primidone, phenobarbital, phenytoin, carbamazepine with its two major metabolites carbamazepine-10,11-epoxide and carbamazepine-10,11-(trans)-dihydrodiol and the new AEDs lamotrigine, hydroxycarbazepine (active metabolite of oxcarbazepine) and zonisamide in serum by high performance liquid chromatography (HPLC)-diode array detector (DAD). After solid-phase extraction, separation is achieved on an Alltima 3C18 analytical column using isocratic elution with a mixture of acetonitrile, methanol and phosphate buffer at 45 degrees C. The method is exhaustively validated, including experimental design in combination with statistical evaluation (ANOVA) to study the robustness of chromatography and sample preparation. Commonly co-administered antiepileptic drugs do not interfere with the method. Intra-day precision (RSD<1.9%), linearity, lower limit of quantitation (LOQ<0.065 mg/l) and robustness make the method suitable for daily therapeutic drug monitoring and pharmacokinetic studies.
authors.affiliation: Epilepsy Institute of the Netherlands (SEIN), Heemstede, The Netherlands.
authors.forename: T A C
authors.initials: TA
authors.lastname: Vermeij
authors.forename: P M
authors.initials: PM
authors.lastname: Edelbroek
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000097:blood*; D002220:Carbamazepine / Q000031:analogs & derivatives / Q000097:blood; D002417:Cattle; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D016903:Drug Monitoring / Q000295:instrumentation / Q000379:methods*; D005013:Ethosuximide / Q000097:blood; D006801:Humans; D007555:Isoxazoles / Q000097:blood; D000077213:Lamotrigine; D000078330:Oxcarbazepine; D010634:Phenobarbital / Q000097:blood; D010672:Phenytoin / Q000097:blood; D011324:Primidone / Q000097:blood; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction / Q000379:methods; D012996:Solutions; D013048:Specimen Handling / Q000379:methods; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature; D014227:Triazines / Q000097:blood; D014635:Valproic Acid / Q000097:blood; D000078305:Zonisamide
chemical_list: D000927:Anticonvulsants; D007555:Isoxazoles; D012996:Solutions; D014227:Triazines; D011324:Primidone; D002220:Carbamazepine; D000078305:Zonisamide; D005013:Ethosuximide; D014635:Valproic Acid; D010672:Phenytoin; D000077213:Lamotrigine; D000078330:Oxcarbazepine; D010634:Phenobarbital