Rapid Quantification of Gabapentin, Pregabalin, and Vigabatrin in Human Serum by Ultraperformance Liquid Chromatography With Mass-Spectrometric Detection

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. Sample pretreatment consisted of adding 20 μL of trichloroacetic acid (...

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Bibliographic Details
Published in:	Therapeutic drug monitoring Vol. 35; no. 1; pp. 48 - 53
Main Authors:	CHAHBOUNI, Abdel, SINJEWEL, Arno, DEN BURGER, Jeroen C. G, VOS, René M, WILHELM, Abraham J, VELDKAMP, Agnes I, SWART, Eleanora L
Format:	Journal Article
Language:	English
Published:	Hagerstown, MD Lippincott Williams & Wilkins 01-02-2013 Lippincott Williams & Wilkins Ovid Technologies
Subjects:	Amines - blood Anticonvulsants - blood Biological and medical sciences Blood Chemical Analysis - methods Chromatography Chromatography, High Pressure Liquid - methods Convulsions & seizures Cyclohexanecarboxylic Acids - blood Drug Stability Drug use Epilepsy gamma-Aminobutyric Acid - analogs & derivatives gamma-Aminobutyric Acid - blood Humans Mass spectrometry Medical sciences Pharmacology Pharmacology. Drug treatments Pregabalin Tandem Mass Spectrometry - methods Vigabatrin - blood Human Biological fluid LC―MS 4-Aminobutyrate transaminase Gabapentin Enzyme Transferases Enzyme inhibitor HPLC chromatography Exploration Anticonvulsant Liquid chromatography Pregabalin Analgesic Vigabatrin Transaminases Serum Diagnosis Detection Mass spectrometry
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Summary:	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. 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. 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. 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0163-4356 1536-3694
DOI:	10.1097/FTD.0b013e31827788c0