A practical, sensitive, and robust UPLC–MS/MS method was developed and validated to quantify lacosamide in human plasma. A simple one‐step protein precipitation was used to extract lacosamide and labeled lacosamide‐13C, D3 as an internal standard (IS) from 150‐μL plasma. The extracts were analyzed on an Eclipse Plus C18 column (50 × 2.1 mm, 1.8 μm) using 0.1% formic acid in water and methanol:acetonitrile (50:50, v/v) under gradient conditions. The extracts were quantified on LCMS‐8040 using electrospray ionization source operated in positive ionization and multiple reaction monitoring modes. The method showed good linearity from 0.02 to 20 μg/mL, which was adequate to cover lacosamide concentration assayed in formulations with different strengths. The bioanalytical assay was fully validated as per current regulatory guidelines. The intra‐batch and inter‐batch precision values of lacosamide were less than 4.6%. Lacosamide was found to be stable at different storage conditions. The extraction recoveries and IS‐normalized matrix factors for lacosamide ranged from 97.17 to 99.68% and from 0.973 to 1.012, respectively. The validated method was successfully applied to a pharmacokinetic study with three lacosamide formulations (50, 100, and 200 mg) in 36 healthy subjects. The assay reliability was determined by reanalysis of 81 subject samples.

中文翻译：

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使用UPLC-MS / MS对人血浆中的拉考酰胺进行选择性定量：应用于不同剂量健康受试者的药代动力学研究。

开发并验证了一种实用，灵敏且稳定的UPLC-MS / MS方法，用于定量测定人血浆中的拉可酰胺。使用简单的一步蛋白沉淀法从150μL血浆中提取拉可酰胺和标记的拉可酰胺13C，D3作为内标（IS）。在Eclipse Plus C18色谱柱（50×2.1 mm，1.8μm）上使用0.1％的甲酸水溶液和甲醇：乙腈（50:50，v / v）在梯度条件下分析提取物。使用在正电离和多种反应监测模式下运行的电喷雾电离源，在LCMS-8040上对提取物进行定量。该方法显示出0.02至20μg/ mL的良好线性，足以覆盖不同强度制剂中测定的拉考酰胺浓度。根据现行法规指南，对生物分析测定法进行了充分验证。拉考酰胺的批内和批间精密度值均小于4.6％。发现Lacosamide在不同的储存条件下是稳定的。拉可酰胺的提取回收率和IS归一化矩阵因子分别为97.17至99.68％和0.973至1.012。验证的方法已成功应用于36种健康受试者的三种拉考酰胺制剂（50、100和200 mg）的药代动力学研究。通过重新分析81个受试者样品来确定测定的可靠性。验证的方法已成功应用于36种健康受试者的三种拉考酰胺制剂（50、100和200 mg）的药代动力学研究。通过重新分析81个受试者样品来确定测定的可靠性。验证的方法已成功应用于36种健康受试者的三种拉考酰胺制剂（50、100和200 mg）的药代动力学研究。通过重新分析81个受试者样品来确定测定的可靠性。