title: Simultaneous analysis of 22 antiepileptic drugs in postmortem blood, serum and plasma using LC-MS-MS with a focus on their role in forensic cases.
abstract: In recent years, there has been a growth in reports of antiepileptic drugs (AEDs) being misused on their own or in combination with other drugs of abuse in a variety of toxicological case types such as drug abuse, suicide, overdose and drug facilitated crime. To our knowledge, there are no simultaneous quantification methods for the analysis of the most commonly encountered AEDs in postmortem whole blood and clinical plasma/serum samples at the same time. A simple, accurate and cost-effective liquid chromatography-tandem mass spectrometric (LC-MS-MS) method has been developed and validated for the simultaneous quantification of carbamazepine (CBZ) and its metabolite CBZ-10,11-epoxide, eslicarbazepine acetate, oxcarbazepine and S-licarbazepine as a metabolite, gabapentin, lacosamide, lamotrigine, levetiracetam, pregabalin, phenobarbital, phenytoin and its metabolite 5-(p-hydroxyphenyl)-5-phenylhydantoin, retigabine (ezogabine) and its metabolite N-acetyl retigabine, rufinamide, stiripentol, topiramate, tiagabine, valproic acid, vigabatrin and zonisamide in postmortem whole blood, serum and plasma which would be suitable for routine forensic toxicological analysis and therapeutic drug monitoring. All AEDs were detected and quantified within 17 min without endogenous interferences. The correlation coefficient (R(2)) was >0.995 for all AEDs with accuracy ranging from 90 to 113% and precision <13% for all analytes. The recovery ranged from 70 to 98%. No carryover was observed in a blank control injected after the highest standard and the matrix effect was acceptable and ranged from 90 to 120%. The method has been successfully verified using authentic case samples that had previously been quantified using different methods.
authors.affiliation: Forensic Medicine and Science, University of Glasgow, University Avenue, Glasgow G12 8QQ, UK shaza.deeb@formed.gla.ac.uk.
authors.forename: Shaza
authors.initials: S
authors.lastname: Deeb
authors.affiliation: Forensic Medicine and Science, University of Glasgow, University Avenue, Glasgow G12 8QQ, UK.
authors.forename: Denise A
authors.initials: DA
authors.lastname: McKeown
authors.affiliation: Forensic Medicine and Science, University of Glasgow, University Avenue, Glasgow G12 8QQ, UK.
authors.forename: Hazel J
authors.initials: HJ
authors.lastname: Torrance
authors.affiliation: Forensic Medicine and Science, University of Glasgow, University Avenue, Glasgow G12 8QQ, UK.
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Wylie
authors.affiliation: NMS Labs, 3701 Welsh Road, Willow Grove, PA 18901, USA.
authors.forename: Barry K
authors.initials: BK
authors.lastname: Logan
authors.affiliation: Forensic Science, Arcadia University, Glenside, PA, USA.
authors.forename: Karen S
authors.initials: KS
authors.lastname: Scott
mesh_terms: D000588:Amines / Q000097:blood; D000927:Anticonvulsants / Q000097:blood*; D002220:Carbamazepine / Q000031:analogs & derivatives / Q000097:blood; D002853:Chromatography, Liquid / Q000379:methods*; D003509:Cyclohexanecarboxylic Acids / Q000097:blood; D016903:Drug Monitoring; D005632:Fructose / Q000031:analogs & derivatives / Q000097:blood; D000077206:Gabapentin; D006801:Humans; D000077213:Lamotrigine; D000077287:Levetiracetam; D057230:Limit of Detection; D009557:Nipecotic Acids / Q000097:blood; D000078330:Oxcarbazepine; D010672:Phenytoin / Q000097:blood; D010889:Piracetam / Q000031:analogs & derivatives / Q000097:blood; D000069583:Pregabalin; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D000078308:Tiagabine; D000077236:Topiramate; D014227:Triazines / Q000097:blood; D014635:Valproic Acid / Q000097:blood; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D009557:Nipecotic Acids; D014227:Triazines; D000077236:Topiramate; D005632:Fructose; D002220:Carbamazepine; D000077287:Levetiracetam; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; D010672:Phenytoin; D000077206:Gabapentin; D000077213:Lamotrigine; D000078330:Oxcarbazepine; D000078308:Tiagabine; D010889:Piracetam