Stepwise optimization approach for improving LC-MS/MS analysis of zwitterionic antiepileptic drugs with implementation of experimental design
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2013
Authors
Kostić, NadaDotsikas, Yannis

Malenović, Anđelija

Jančić-Stojanović, Biljana

Rakić, Tijana
Ivanović, Darko
Medenica, Mirjana
Article (Published version)

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In this article, a step-by-step optimization procedure for improving analyte response with implementation of experimental design is described. Zwitterionic antiepileptics, namely vigabatrin, pregabalin and gabapentin, were chosen as model compounds to undergo chloroformate-mediated derivatization followed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analysis. Application of a planned stepwise optimization procedure allowed responses of analytes, expressed as areas and signal-to-noise ratios, to be improved, enabling achievement of lower limit of detection values. Results from the current study demonstrate that optimization of parameters such as scan time, geometry of ion source, sheath and auxiliary gas pressure, capillary temperature, collision pressure and mobile phase composition can have a positive impact on sensitivity of LC-MS/MS methods. Optimization of LC and MS parameters led to a total increment of 53.9%, 83.3% and 95.7% in areas of derivatized vi...gabatrin, pregabalin and gabapentin, respectively, while for signal-to-noise values, an improvement of 140.0%, 93.6% and 124.0% was achieved, compared to autotune settings. After defining the final optimal conditions, a time-segmented method was validated for the determination of mentioned drugs in plasma. The method proved to be accurate and precise with excellent linearity for the tested concentration range (40.0ngml(-1)-10.0x10(3)ngml(-1)). Copyright
Keywords:
optimization / antiepileptics / ion source parameters / experimental design / response surface methodologySource:
Journal of Mass Spectrometry, 2013, 48, 7, 875-884Publisher:
- Wiley-Blackwell, Hoboken
Projects:
- Modelling of different chromatographic systems with chemometrical approach in pharmaceutical analysis (RS-172052)
DOI: 10.1002/jms.3236
ISSN: 1076-5174
PubMed: 23832944