摘要
目的建立测定血浆中奥卡西平活性代谢产物10-羟基卡马西平（10-hydroxycarbazepine,MHD）的高效液相色谱方法并评价其血药浓度与疗效的关系。方法以6-甲氧基水杨酸为内标,用乙酸乙酯对血浆样本进行提取。采用Symmetry ShieldRP18（4.6×250 mm,5μm）色谱柱,流动相为乙腈：0.05%甲酸水溶液（23∶77,v/v）,流速为1.0 m L/min,检测波长214 nm,柱温40℃。收集服用奥卡西平片的门诊和住院癫痫患者78例108个稳态浓度血样,以高效液相色谱法（high performance liquid chromatography-UV,HPLC-UV）测定MHD血药浓度,参照疗效评定标准评价血药浓度与疗效关系。结果 MHD浓度在0.4~40μg/m L（r=0.998）线性关系良好,定量下限是0.4μg/m L。日内、日间RSD值均为〈15.0%,MHD提取回收率在75.1%~78.5%,内标提取回收率为86.5%。癫痫患者血药浓度监测结果发现,服药后2 h左右血浆药物浓度达到峰值,不同患者之间的血药浓度存在较大的差异。结论该HPLC方法简便、准确、灵敏度高,可应用于临床对服用奥卡西平患者进行MHD血药浓度监测。MHD的谷浓度控制在大于8μg/m L的浓度范围时对大多数癫痫患者能够起效。
Objective To develop an HPLC method for the determination of 10-hydroxycarbamazepine（ MHD） of oxcarbazepine active metabolite in human plasma and evaluate the relationship between concentration and efficacy. Methods Using 6-methoxysalicylic acid as internal standard,MHD was extracted by ethyl acetate. A Symmetry ShiledTMRP18column（ 4. 6 × 250 mm,5 μm） was used,with the mobile phase of acetonitrile and water containing 0. 05% formic acid（ v / v,23∶77） at the detection wavelength of 214 nm. The flow rate was 1. 0 m L / min and the column temperature was 40℃. Measured concentrations of MHD from 108 blood samples of 78 epileptic patients by HPLC-UV,and all corresponding clinical data were collected from the medical records of the population. The relationship between serum concentration and clinical efficacy was evaluated by assessing curative effect criterion. Results The calibration curve was linear in the range of 0. 4 ~ 40 μg / m L（ r = 0. 998） and the detection limit was 0. 4 μg / m L. The RSD of intra-and inter-day precision was both less than 15%. The range of extraction recovery ratio of MHD was 75. 1% ~ 78. 5%. Extraction recovery ratio of internal standard was 86. 5%. The results of therapeutic drug concentration monitoring（ TDM） for MHD showed that after taking epilepsy about 2 h,plasma drug concentration reached its peak,there was a large difference between different patients blood drug concentration. Conclusion The method is simple,accurate,sensitive. It is suitable for clinical to study MHD blood concentration monitioring of patients after taking OXC. It is more effective for most patients with epilepsy that the therapeutic drug concentration of MHD is higher than 8 μg / m L.
出处
《中国生化药物杂志》
CAS
2015年第1期106-109,共4页
Chinese Journal of Biochemical Pharmaceutics
基金
苏州市科技计划项目(SYSD2012129)
