拉考沙胺血药浓度的测定及其与抗癫痫治疗效果相关性研究OA

AIM To develop a liquid chromatography-tandem mass spectrometry(LC-MS/MS)method for determining lacosamide(LCM)plasma concentrations,and to analyze the correlation between LCM plasma concentrations and the antiepileptic therapy efficacy,thereby providing a reference for clinical dosage adjustment.METHODS Plasma samples were pretreated by protein precipitation with acetonitrile,using dexmedetomidine as the internal standard.Separation was achieved on a C18 column using a mobile phase of 0.2％formic acid in water and acetonitrile with gradient elution at a flow rate of 0.5 mL·min-1.The column temperature was set at 40℃,and the injection volume was 2 μL.The validated method was used to determine the steady-state trough concentrations of LCM in 128 epilepsy patients receiving regular LCM therapy.Patient demographics,clinical efficacy,and the occurrence of adverse drug reactions were collected for correlation analysis.RESULTS The method demonstrated good linearity within the concentration range of 0.50-50.00 μg·mL-1,with high accuracy and stability.The LCM plasma concentration in the 128 patients was(8.66±5.11)μg·mL-1.Three patients(2.34％)had concentrations below 1 μg·mL-1,31 patients(24.22％)had concentrations above 10 μg·mL-1,and 94 patients(73.44％)had concentrations within the recommended therapeutic range of 1-10 μg·mL-1.At the same dosage,the plasma concentration showed a moderate negative correlation with total body weight and a weak negative correlation with body mass index.No significant difference in plasma concentration was observed between the treatment-effective group and the treatment-ineffective group.However,the plasma concentration in the group experiencing adverse reactions was significantly higher than that in the group without adverse reactions[(11.90±6.03)μg·mL-1 vs(7.99±4.68)μg·mL-1,P＜0.01].CONCLUSION This study successfully established a rapid,accurate,and reliable LC-MS/MS method suitable for the TDM of LCM.Clinical application analysis indicated that under standardized dosing,most patients achieved plasma concentrations within the therapeutic range.In comparison to body mass index,the plasma concentration of lacosamide demonstrates a stronger correlation with body weight.