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Vigabatrin in dried plasma spots: validation of a novel LC-MS/MS method and application to clinical practice.

Journal of chromatography. B, Analytical technologies in the biomedical and life sciences (2014-06-09)
Nađa Kostić, Yannis Dotsikas, Nebojša Jović, Galina Stevanović, Anđelija Malenović, Mirjana Medenica
ABSTRACT

This paper presents a LC-MS/MS method for the determination of antiepileptic drug vigabatrin in dried plasma spots (DPS). Due to its zwitterionic chemical structure, a pre-column derivatization procedure was performed, aiming to yield enhanced ionization efficiency and improved chromatographic behaviour. Propyl chloroformate, in the presence of propanol, was selected as the best derivatization reagent, providing a strong signal along with reasonable run time. A relatively novel sample collection technique, DPS, was utilized, offering easy sample handling and analysis, using a sample in micro amount (∼5μL). Derivatized vigabatrin and its internal standard, 4-aminocyclohexanecarboxylic acid, were extracted by liquid-liquid extraction (LLE) and determined in positive ion mode by applying two SRM transitions per analyte. A Zorbax Eclipse XDB-C8 column (150×4.6mm, 5μm particle size) maintained at 30°C, was utilized with running mobile phase composed of acetonitrile: 0.15% formic acid (85:15, v/v). Flow rate was 550μL/min and total run time 4.5min. The assay exhibited excellent linearity over the concentration range of 0.500-50.0μg/mL, which is suitable for the determination of vigabatrin level after per os administration in children and youths with epilepsy, who were on vigabatrin therapy, with or without co-medication. Specificity, accuracy, precision, recovery, matrix-effect and stability were also estimated and assessed within acceptance criteria.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Acetonitrile, suitable for HPLC, gradient grade, ≥99.9%
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Acetonitrile, anhydrous, 99.8%
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Pyridine, anhydrous, 99.8%
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Acetonitrile, HPLC Plus, ≥99.9%
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Ethyl acetate, ACS reagent, ≥99.5%
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Chloroform, contains 100-200 ppm amylenes as stabilizer, ≥99.5%
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Ethyl acetate, suitable for HPLC, ≥99.7%
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Ethyl acetate, anhydrous, 99.8%
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Formic acid, reagent grade, ≥95%
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Chloroform, anhydrous, ≥99%, contains 0.5-1.0% ethanol as stabilizer
Sigma-Aldrich
Acetonitrile, ACS reagent, ≥99.5%
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Chloroform, anhydrous, contains amylenes as stabilizer, ≥99%
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Formic acid, puriss. p.a., ACS reagent, reag. Ph. Eur., ≥98%
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Pyridine, ACS reagent, ≥99.0%
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1-Propanol, suitable for HPLC, ≥99.9%
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Chloroform, suitable for HPLC, ≥99.8%, contains 0.5-1.0% ethanol as stabilizer
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Chloroform, HPLC Plus, for HPLC, GC, and residue analysis, ≥99.9%, contains amylenes as stabilizer
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Formic acid, ACS reagent, ≥96%
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Acetonitrile, suitable for HPLC, gradient grade, ≥99.9%
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Ethyl acetate, HPLC Plus, for HPLC, GC, and residue analysis, 99.9%
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Acetonitrile solution, contains 0.1 % (v/v) trifluoroacetic acid, suitable for HPLC
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1-Propanol, anhydrous, 99.7%
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Formic acid, puriss., meets analytical specifications of DAC, FCC, 98.0-100%
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Pyridine, suitable for HPLC, ≥99.9%
Sigma-Aldrich
Chloroform, contains ethanol as stabilizer, ACS reagent, ≥99.8%
Sigma-Aldrich
1-Propanol, ACS reagent, ≥99.5%
Sigma-Aldrich
Ethyl acetate, puriss., meets analytical specification of Ph. Eur., BP, NF, ≥99.5% (GC)
Sigma-Aldrich
Pyridine, ReagentPlus®, ≥99%
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Chloroform, suitable for HPLC, ≥99.8%, amylene stabilized
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Formic acid, ACS reagent, ≥88%