Quantification of new antiepileptic drugs by liquid chromatography/electrospray ionization tandem mass spectrometry and its application to cellular uptake experiment using human placental choriocarcinoma BeWo cells

Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Ayako FurugenKen Iseki

Abstract

A method for quantification of new antiepileptic drugs, including lamotrigine (LTG), levetiracetam (LEV), gabapentin (GBP), and topiramate (TPM), in cellular samples, using liquid chromatography/electrospray ionization tandem mass spectrometry was developed to better understand the membrane transport mechanisms of these drugs. Cell lysate was deproteinized by methanol containing LEV-d3 as an internal standard (IS). Chromatographic separation was performed on a C18 column using gradient elution with methanol-water-formic acid (10:90:0.1, v/v/v) and methanol-formic acid (100:0.1, v/v). Analytes were detected in positive ion electrospray mode with selected reaction monitoring (SRM). This method was applicable for a linear range of 5 to 500pmol for LTG; 5 to 1000pmol for LEV; 10 to 10,000pmol for GBP; and 5 to 5000pmol for TPM. The intra-day precision, inter-day precision, and accuracy data were assessed and found to be acceptable. This developed and validated method was then successfully applied to the investigation of uptake of the new antiepileptic drugs in placental choriocarcinoma BeWo cells. The intracellular concentration of these drugs in BeWo cells, accumulating over 30min at 37°C was in the order of GBP>LTG>LEV≈TPM. Furth...Continue Reading

References

Aug 16, 2011·Journal of Pharmaceutical and Biomedical Analysis·Kwon-Bok KimJae-Gook Shin
Apr 10, 2013·Biochemical Pharmacology·David DickensMunir Pirmohamed
Sep 12, 2013·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Li WangDouglas H Sweet

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Citations

Oct 2, 2020·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Ayako Furugen

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