Development of a sensitive bioanalytical method for the quantification of lacosamide in rat plasma. Application to preclinical pharmacokinetics studies in rats.

Arzneimittel-Forschung-Drug Research Pub Date : 2012-05-01 Epub Date: 2012-03-01 DOI:10.1055/s-0032-1301911
S Shah, S G Vasantharaju, K Arumugam, B S Muddukrishna, N Desai
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引用次数: 8

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.

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大鼠血浆中拉科沙胺的灵敏生物分析方法的建立。应用于大鼠临床前药代动力学研究。
建立了一种灵敏、选择性的高效液相色谱法测定大鼠血浆中拉科沙胺的含量。优化了从大鼠血浆中提取拉科沙胺的液液萃取工艺。色谱分离采用反相C18 Hichrom (250×4.6 mm, 5µm)柱,流动相为乙腈-磷酸缓冲液(pH 3.2±0.1;20mm) (21:79, v/v),流速为1ml /min。日内、日间测定精密度和准确度均低于15% CV。拉科沙胺的定量下限为25 ng/mL,在25 ~ 10000 ng/mL浓度范围内呈线性关系。该方法已成功用于拉科沙胺在大鼠体内的临床前药代动力学研究。
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