Quantitation of pregabalin in dried blood spots and dried plasma spots by validated LC-MS/MS methods
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2015
Authors
Kostić, NadaDotsikas, Yannis

Jović, Nebojša
Stevanović, Galina
Malenović, Anđelija

Medenica, Mirjana
Article (Published version)

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In this paper, novel LC-MS/MS methods for the determination of antiepileptic drug pregabalin in dried matrix spots (DMS) are presented. This attractive technique of sample collection in micro amount was utilized in the form of dried blood spots (DBS) and dried plasma spots (DPS). Following a pre-column derivatization procedure, using n-propyl chloroformate in the presence of n-propanol, and consecutive liquid-liquid extraction, derivatized pregabalin and its internal standard, 4-aminocyclohexanecarboxylic acid, were detected in positive ion mode by applying two SRM transitions per analyte. A YMC-Pack Octyl column (50 mm x 4.0 mm, 3 mu m particle size) maintained at 30 degrees C, was utilized with running mobile phase composed of acetonitrile: 0.15% formic acid (85:15, v/v). Flow rate was 550 mu L/min and total run time 2 min. Established methods were fully validated over the concentration range of 0.200-20.0 mu g/mL for DBS and 0.400-40.0 mu g/mL for DPS, respectively, while specificit...y, accuracy, precision, recovery, matrix-effect, stability, dilution integrity and spot homogeneity were found within acceptance criteria. Validated methods were applied for the determination of pregabalin levels in dried blood and plasma samples obtained from patients with epilepsy, after per os administration of commercial capsules. Comparison of drug level in blood and plasma, as well as correction steps undertaken in order to overcome hematocrit issue, when analyzing DBS, are also given.
Keywords:
Pregabalin / Chloroformates / Dried blood/plasma spots / Mass spectrometry / HematocritSource:
Journal of Pharmaceutical and Biomedical Analysis, 2015, 109, 79-84Publisher:
- Elsevier Science BV, Amsterdam
Projects:
- Modelling of different chromatographic systems with chemometrical approach in pharmaceutical analysis (RS-172052)
DOI: 10.1016/j.jpba.2015.02.023
ISSN: 0731-7085
PubMed: 25767905