HPLC方法测定人血清拉莫三嗪浓度及其在临床治疗药物监测中的应用  

Determination of Lamotrigine in Human Serum by HPLC and Its Application for Clinical Therapeutic Drug Monitoring

作　　者：朱永坚[1,2] 黄文灿[1,2] 倪晓佳[1,2] 张明[1,2] 王占璋[1,2] 卢浩扬[1,2] 胡晋卿[1,2] 邓书华[1,2] 朱秀清[1,2] 邱畅[1,2] 温预关[1,2] 尚德为[1,2] 

机构地区：[1]广州市惠爱医院 [2]广州医科大学附属脑科医院,广东广州510370

出　　处：《今日药学》2015年第7期473-475,478,共4页Pharmacy Today

基　　金：国家自然科学基金(81403016);广州市医药卫生科技项目(20141A011041);广州市脑科医院广州市医学重点学科建设项目子项目(GBH2014-ZD07)

摘　　要：目的建立HPLC法测定人血清中拉莫三嗪（LTG）血药浓度,并应用于临床监测拉莫三嗪治疗癫痫与双向情感障碍血药浓度。方法以吡非尼酮作内标,甲醇作为蛋白沉淀剂处理血清样本,色谱柱Eclipse plus C18柱,流动相为甲醇与5 mmo L/L甲酸铵水（52∶48,v/v）,流速为0.8 mL/min,柱温40.0℃,检测波长：310 nm。临床收集未服用LTG患者血样,并比较LTG给药后在抗癫痫和治疗双向情感障碍有效浓度的范围。结果 LTG在0.5-20μg/mL范围内线性关系良好,低中高3个浓度质控样本的日内精密度均小于6.8%,日间精密度小于13.64%,提取回收率大于91.24%。LTG治疗双相情感障碍血药浓度为（2.16±0.97）μg/mL,剂量校正血药浓度为（18.88±11.86）ng/（m L·mg）;抗癫痫血药浓度为（3.63±2.59）μg/mL,剂量校正血药浓度为（25.80±14.97）ng/（m L·mg）。结论使用该方法可准确、灵敏地测定拉莫三嗪血药浓度,可应用于LTG临床血药浓度测定。OBJECTIVE To establish a rapid determination method for lamotrigine（ LTG） in human serum with high performance liquid chromatography（ HPLC）,and apply it to the treatment of epilepsy and bipolar by clinical therapeutic drug monitoring.METHODS Using pirfenidone as internal standard,with methanol as protein precipitator,LTG was analyzed with a HPLC system（ Eclipse plus C18 column,150 mm×4.6 mm,5 μm） with the mobile phase of methanol ： 5 mmol / L ammonium formate in water（ 52 ∶48,v / v） at a flow rate of 0.8 mL / min,the column temperature of 40 ℃,the detection wavelength at 310 nm,and the inject volume of10 μL. The blood samples from the patients taking LTG under fasting were detected by the validated method. The effective ranges of LTG concentrations were compared between the patients with epilepsy and bipolar. RESULTS The concentrations of LTG in serum were linear in the range of 0.5-20 μg / mL. The recoveries of LTG in the low,middle and high quality controls were over 91.24%. The withinday（ n = 5） precisions were less than 6. 8%,and the between-day（ n = 3） precisions were less than 13. 64%. The average LTG concentration in the patients with bipolar disorders was（ 2. 16 ± 0. 97） μg / mL while the dose-normalized concentration was（ 18. 88 ±11. 86） ng /（ m L· mg）; in the antiepileptic treatment,the average LTG concentration was（ 3. 63 ± 2. 59） μg / mL,while the dosenormalized concentration was（ 25.80±14. 97） ng /（ mL · mg）. CONCLUSION The validated method provides a sensitive,precise and reliable analytical procedure for clinical monitoring of LTG,which can be applied for drug concentration determination.

关 键 词：高效液相色谱法 拉莫三嗪 治疗药物监测 抗癫痫药 情感稳定剂 

分 类 号：R927[医药卫生—药学]