title: Rapid quantification of gabapentin, pregabalin, and vigabatrin in human serum by ultraperformance liquid chromatography with mass-spectrometric detection.
abstract: BACKGROUND
  Gabapentin (GBP), pregabalin (PRG), and vigabatrin (VIG) are used for the prevention and treatment of epileptic seizures. The developed method was applied to samples from subjects participating in a pharmacokinetic study of GBP.
  
  
  METHODS
  Sample pretreatment consisted of adding 20 μL of trichloroacetic acid (30%; vol/vol) and 200 μL of GBP-d4 in acetonitrile as an internal standard to 20 μL of serum. Chromatographic separation was performed on an Acquity separation module using a Kinetex RP18 column. The aqueous and organic mobile phases were 2 mM ammonium acetate supplemented with 0.1% formic acid in water and acetonitrile, respectively. The detection by a tandem quadrupole mass spectrometer, operating in the positive mode using multiple reaction monitoring, was completed within 2 minutes.
  
  
  RESULTS
  The method was linear over the range of 0.03-25 mg/L for GBP, 0.03-25 mg/L for PRG, and 0.06-50 mg/L for VIG. The between- and within-run accuracies ranged from 90% to 107%. The between- and within-run imprecisions of the method were <10%. Stability data show no significant decrease of the analytes. A relative matrix effect of -1%, 0.2%, and -5% was determined for GBP, PRG, and VIG, respectively.
  
  
  CONCLUSIONS
  A simple and sensitive ultraperformance liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous quantification of GBP, PRG, and VIG in human serum. The reported method provided the necessary linearity, precision, and accuracy to allow the determination of GBP, PRG, and VIG for therapeutic drug monitoring and clinical research purposes.
authors.affiliation: Department of Clinical Pharmacology and Pharmacy, VU University Medical Center, Amsterdam, The Netherlands. a.chahbouni@vumc.nl
authors.forename: Abdel
authors.initials: A
authors.lastname: Chahbouni
authors.forename: Arno
authors.initials: A
authors.lastname: Sinjewel
authors.forename: Jeroen C G
authors.initials: JC
authors.lastname: den Burger
authors.forename: René M
authors.initials: RM
authors.lastname: Vos
authors.forename: Abraham J
authors.initials: AJ
authors.lastname: Wilhelm
authors.forename: Agnes I
authors.initials: AI
authors.lastname: Veldkamp
authors.forename: Eleanora L
authors.initials: EL
authors.lastname: Swart
mesh_terms: D000588:Amines / Q000097:blood*; D000927:Anticonvulsants / Q000097:blood*; D001774:Blood Chemical Analysis / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003509:Cyclohexanecarboxylic Acids / Q000097:blood*; D004355:Drug Stability; D000077206:Gabapentin; D006801:Humans; D000069583:Pregabalin; D053719:Tandem Mass Spectrometry / Q000379:methods; D020888:Vigabatrin / Q000097:blood*; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D020888:Vigabatrin