High-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) has become a primary analytical methodology in therapeutic drug monitoring of antiepileptic drugs (AEDs). To demonstrate the utility of LC-MS/MS in measuring drug concentrations in serum or plasma, analysis of lacosamide (Vimpat) is discussed in this chapter. Lacosamide is an example of the newer-generation AEDs. The drug is extracted by protein precipitation and dilution of the serum specimen. A small volume of the extracted specimen is injected into a reversed-phase chromatography column, and lacosamide is identified by positive electrospray ionization (ESI) mass spectrometry in the multiple reaction monitoring (MRM) mode, which provides selectivity for quantitative analysis. A deuterated internal standard is used to correct for any loss of analyte during the process of extraction and analysis. A seven-point calibration curve and two levels of quality controls are included in each batch.
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