Development of a Sensitive Bioanalytical Method for the Quantification of Lacosamide in Rat Plasma. Application to Preclinical Pharmacokinetics Studies in Rats

Abstract

A sensitive and selective high performance liquid chromatographic (HPLC) method was developed and validated for quantification of lacosamide in rat plasma. A liquid-liquid extraction procedure was optimized to extract lacosamide from rat plasma. Chromatographic separation was accomplished using a reversed phase C18 Hichrom (250×4.6 mm, 5 µm) column with the mobile phase consisting of acetonitrile-phosphate buffer (pH 3.2±0.1; 20 mM) (21:79, v/v) at a flow rate of 1 mL/min. Both intra- and inter day assay precision and accuracy were lower than 15% CV. The lower limit of quantitation was 25 ng/mL for lacosamide and the response was linear in a concentration range from 25 to 10 000 ng/mL. The developed method was successfully used for the preclinical pharmacokinetic study of lacosamide in rats.

A fully validated method for the determination of lacosamide in human plasma using gas chromatography with mass spectrometry: Application for therapeutic drug monitoring

“…In the pretreatment step of biological samples, the previous studies have used mainly LLE or direct injection after protein precipitation . The direct injected samples after protein precipitation are mainly used for LC analysis and they usually show high matrix effect and significant signal suppression .…”

“…All published methods for the determination of lacosamide in biological samples use LC . To our knowledge, there is no validated method in the literature for the determination of lacosamide using GC–MS.…”

Selective quantification of lacosamide in human plasma using UPLC–MS/MS: Application to pharmacokinetic study in healthy subjects with different doses

“…Several methods have been reported to determine lacosamide as a single analyte (Devi, Varma, Rani, & Srinivas, 2014; D'Urso, Ricotta, & de Grazia, 2017; Kestelyn et al, 2011; Kim, Koo, et al, 2012; Korman, Langman, & Jannetto, 2015; Martinez et al, 2012; Nikolaou, Papoutsis, Spiliopoulou, Voudris, & Athanaselis, 2015; Shah, Vasantharaju, Arumugam, Muddukrishna, & Desai, 2012), with its major metabolite desmethyl lacosamide (Payto, Foldvary‐Schaefer, So, Bruton, & Wang, 2014), and in presence of other AEDs (Deeb et al, 2014; Gonçalves, Alves, Bicker, Falcão, & Fortuna, 2018; Kuhn & Knabbe, 2013) in various biological matrices. Different analytical techniques such as immunoassay (D'Urso et al, 2017), GC–MS (Nikolaou et al, 2015), HPLC with ultraviolet detection (Devi et al, 2014; Kestelyn et al, 2011; Martinez et al, 2012; Shah et al, 2012), photodiode array detection (Gonçalves et al, 2018), and MS/MS (Deeb et al, 2014; D'Urso et al, 2017; Kim, Gu, et al, 2012; Korman et al, 2015; Payto et al, 2014) have been used for its determination. Kuhn and Knabbe (2013) have reported a UPLC–MS/MS method for the simultaneous measurement of six AEDs in serum and plasma samples.…”

Determination of lacosamide in human plasma by LC–MS/MS and its application to a human pharmacokinetic study

“…According to literature, only a few methods were reported for the determination of LCA in biological samples using HPLC [7], GC–MS [8], and LC–MS/MS [9–12]. Greenaway [7] et al proposed an HPLC method and Nikolaou et al developed a GC‐MS [8] method for determination of LCA in epileptic patients as well as in spiked human plasma, however, these methods have not used deuterated compound as Internal standard, which cannot eliminate the variability in results, reproducibility and moreover the run time also high.…”